東北大学研究者紹介

研究者詳細

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カワカミ　ヒサト

川上　尚人

Hisato Kawakami

所属

大学院医学系研究科　医科学専攻　内科病態学講座（臨床腫瘍学分野）

職名

教授

学位

医学博士（近畿大学大学院）

researchmap

https://researchmap.jp/kawakami_h

J-GLOBAL ID

201401095897691603

プロフィール

日本内科学会認定医／総合内科専門医／指導医

日本臨床腫瘍学会薬物療法専門医／指導医

日本がん治療認定医

日本消化器病学会専門医

経歴 7

2024年10月～継続中

東北大学　大学院医学系研究科臨床腫瘍学分野　教授
2016年10月～継続中

近畿大学　医学部腫瘍内科
2024年5月～ 2024年10月

近畿大学　医学部　講師
2014年7月～ 2016年9月

Mayo Clinic, Rochester
2010年4月～ 2013年6月

近畿大学　医学部腫瘍内科
2005年5月～ 2010年3月

大阪赤十字病院　消化器科
2004年3月～ 2005年4月

京都大学医学部附属病院

︎全件表示 ︎最初の5件までを表示

学歴 2

近畿大学大学院　医学部

2010年4月～ 2013年12月
熊本大学　医学部　医学科

1997年4月～ 2003年3月

委員歴 7

日本胃癌学会　倫理委員会委員、Patient Advocacy委員会委員、患者用ガイドライン作成委員会委員、施設認定制度委員会委員、会誌編集委員会委員、ガイドライン作成委員会委員、代議員選挙管理委員会委員

2026年4月～継続中
日本臨床腫瘍学会　理事、評議員、広報渉外委員会委員長、将来構想委員会委員、賞等選考委員会委員

2026年4月～継続中
日本食道学会　用語委員会委員

2024年1月～継続中
大腸癌研究会　大腸癌治療ガイドライン委員

2023年4月～継続中
日本肝胆膵外科学会　転移性肝腫瘍国際診療ガイドライン委員

2019年4月～継続中
厚労科研　「３学会合同「がんゲノムネット」を用いた、国民への「がんゲノム医療」に関する教育と正しい情報伝達に関する研究」分担研究者

～ 2021年3月
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic Oesophageal / Gastric Cancer

2018年～ 2019年12月

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所属学協会 10

European Society for Medical Oncology
American Society of Clinical Oncology
日本遺伝性腫瘍学会
日本食道学会
日本胃癌学会
日本がん分子標的治療学会
日本臨床腫瘍学会
日本消化器内視鏡学会
日本消化器病学会
日本内科学会

︎全件表示 ︎最初の5件までを表示

研究キーワード 4

バイオマーカー
薬物療法
消化器癌
臨床腫瘍学

研究分野 1

ライフサイエンス / 血液、腫瘍内科学 /

受賞 10

中西・中川賞（個人賞）

2026年3月　西日本がん研究機構
第98回胃癌学会総会西記念賞

2026年3月　日本胃癌学会
研究助成金

2026年2月　高松宮妃癌研究基金
課題研究助成金

2023年4月　日本胃癌学会
2021年度 deleteC がん治療研究助成

2022年1月　deleteC　"MSI-H胃がんに対する1次治療としてのニボルマブ＋イピリムマブ併用療法第II相試験（NO LIMIT試験：Nivolumab plus Low dose Ipilimumab In gastric MSI-H Tumor）"
最優秀演題賞

2021年10月　第59回日本癌治療学会学術集会
Harvard Medical School, Global Clinical Scholars Research Training Program: Certificated

2014年6月
海外留学助成金

2014年3月　上原記念生命科学財団
Travel Award

2013年　The 2nd Japan Taiwan Oncology Phase I Conference
奨励賞

2013年　日本臨床腫瘍学会

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論文 219

Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. 国際誌

Yuichiro Doki, Jaffer A Ajani, Ken Kato, Jianming Xu, Lucjan Wyrwicz, Satoru Motoyama, Takashi Ogata, Hisato Kawakami, Chih-Hung Hsu, Antoine Adenis, Farid El Hajbi, Maria Di Bartolomeo, Maria I Braghiroli, Eva Holtved, Sandra A Ostoich, Hye R Kim, Masaki Ueno, Wasat Mansoor, Wen-Chi Yang, Tianshu Liu, John Bridgewater, Tomoki Makino, Ioannis Xynos, Xuan Liu, Ming Lei, Kaoru Kondo, Apurva Patel, Joseph Gricar, Ian Chau, Yuko Kitagawa

The New England journal of medicine　386　(5)　449-462　2022年2月3日

DOI： 10.1056/NEJMoa2111380 　

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BACKGROUND: First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma. METHODS: In this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients). RESULTS: A total of 970 patients underwent randomization. At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P = 0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with tumor-cell PD-L1 expression of 1% or greater (median, 13.7 vs. 9.1 months; hazard ratio, 0.64; 98.6% CI, 0.46 to 0.90; P = 0.001) and in the overall population (median, 12.7 vs. 10.7 months; hazard ratio, 0.78; 98.2% CI, 0.62 to 0.98; P = 0.01). Among patients with tumor-cell PD-L1 expression of 1% or greater, a significant progression-free survival benefit was also seen with nivolumab plus chemotherapy over chemotherapy alone (hazard ratio for disease progression or death, 0.65; 98.5% CI, 0.46 to 0.92; P = 0.002) but not with nivolumab plus ipilimumab as compared with chemotherapy. The incidence of treatment-related adverse events of grade 3 or 4 was 47% with nivolumab plus chemotherapy, 32% with nivolumab plus ipilimumab, and 36% with chemotherapy alone. CONCLUSIONS: Both first-line treatment with nivolumab plus chemotherapy and first-line treatment with nivolumab plus ipilimumab resulted in significantly longer overall survival than chemotherapy alone in patients with advanced esophageal squamous-cell carcinoma, with no new safety signals identified. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 648 ClinicalTrials.gov number, NCT03143153.).
Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. 国際誌

Sachiko Yamamoto, Hisato Kawakami, Takayuki Kii, Hiroki Hara, Ryohei Kawabata, Junji Kawada, Atsushi Takeno, Jin Matsuyama, Shugo Ueda, Yoshihiro Okita, Shunji Endo, Yutaka Kimura, Kazuhiro Yanagihara, Tatsuya Okuno, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

European journal of cancer (Oxford, England : 1990)　154　307-315　2021年9月
出版者・発行元： Elsevier {BV}
DOI： 10.1016/j.ejca.2021.06.035 　

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BACKGROUND: There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive either DTX (70 mg/m2 on day 1 of each 21-day cycle) or PTX (100 mg/m2 on days 1, 8, 15, 22, 29 and 36 of each 49-day cycle). The primary end-point was overall survival (OS), and secondary end-points included progression-free survival (PFS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: Seventy-eight eligible patients (N = 39 in each group) were included for efficacy analysis. OS was significantly longer in the PTX group than in the DTX group (median, 8.8 versus 7.3 months; hazard ratio [HR], 0.62; P = 0.047). A significant benefit of PTX over DTX was also apparent in PFS (median, 4.4 versus 2.1 months; HR, 0.49; P = 0.002) and TTF (median, 3.8 versus 2.1 months; HR, 0.45; P < 0.001). RR (25.6% versus 7.7%, P = 0.065) were higher in the PTX group than in the DTX group. Compared to the PTX group, neutropenia (28% versus 80%) and leukopenia (28% versus 76%) of grade ≥3 as well as febrile neutropenia (0% vs. 46%, P < 0.0001) occurred more frequently in the DTX group. CONCLUSION: PTX showed a significantly better efficacy as well as a more manageable toxicity compared with DTX. CLINICAL TRIAL REGISTRATION: UMIN000007940.
Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. 国際誌

Salvatore Siena, Maria Di Bartolomeo, Kanwal Raghav, Toshiki Masuishi, Fotios Loupakis, Hisato Kawakami, Kensei Yamaguchi, Tomohiro Nishina, Marwan Fakih, Elena Elez, Javier Rodriguez, Fortunato Ciardiello, Yoshito Komatsu, Taito Esaki, Ki Chung, Zev Wainberg, Andrea Sartore-Bianchi, Kapil Saxena, Eriko Yamamoto, Emarjola Bako, Yasuyuki Okuda, Javad Shahidi, Axel Grothey, Takayuki Yoshino

The Lancet. Oncology　22　(6)　779-789　2021年6月

DOI： 10.1016/S1470-2045(21)00086-3 　

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BACKGROUND: HER2 amplification has been identified in 2-3% of patients with colorectal cancer, although there are currently no approved HER2-targeted therapies for colorectal cancer. We aimed to study the antitumour activity and safety of trastuzumab deruxtecan (an antibody-drug conjugate of humanised anti-HER2 antibody with topoisomerase I inhibitor payloads) in patients with HER2-expressing metastatic colorectal cancer. METHODS: DESTINY-CRC01 is an open-label, phase 2 study that recruited patients from 25 clinics and hospitals in Italy, Japan, Spain, the UK, and the USA. Eligible patients had centrally confirmed HER2-expressing metastatic colorectal cancer that had progressed on two or more previous regimens (HER2-targeted therapies other than trastuzumab deruxtecan permitted), were aged 18 years or older (≥20 years in Japan), had an Eastern Cooperative Oncology Group score of 0 or 1, and had RAS and BRAFV600E wild-type tumours. Patients were enrolled into one of three cohorts by HER2 expression level: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC2+ and in-situ hybridisation [ISH]-positive), cohort B (IHC2+ and ISH-negative), or cohort C (IHC1+). Patients received 6·4 mg/kg trastuzumab deruxtecan intravenously every 3 weeks until disease progression, unacceptable adverse events, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate in cohort A by independent central review which was assessed in the full analysis set and safety was assessed in the safety analysis set. Both the full analysis set and the safety analysis set included all patients who received one or more doses of trastuzumab deruxtecan. This ongoing trial is registered with ClinicalTrials.gov, number NCT03384940. FINDINGS: Between Feb 23, 2018, and July 3, 2019, 78 patients were enrolled in the study (53 in cohort A, seven in cohort B, and 18 in cohort C), all of whom received at least one dose of study drug. For the 53 (68%) patients with HER2-positive tumours (cohort A), a confirmed objective response was reported in 24 (45·3%, 95% CI 31·6-59·6) patients after a median follow-up of 27·1 weeks (IQR 19·3-40·1). Grade 3 or worse treatment-emergent adverse events that occurred in at least 10% of all participants were decreased neutrophil count (17 [22%] of 78) and anaemia (11 [14%]). Five patients (6%) had adjudicated interstitial lung disease or pneumonitis (two grade 2; one grade 3; two grade 5, the only treatment-related deaths). INTERPRETATION: Trastuzumab deruxtecan showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with that reported in previous trastuzumab deruxtecan trials. Interstitial lung disease and pneumonitis are important risks requiring careful monitoring and prompt intervention. FUNDING: Daiichi Sankyo.
Folate receptor α increases chemotherapy resistance through stabilizing MDM2 in cooperation with PHB2 that is overcome by MORAb-202 in gastric cancer. 国際誌

Hitomi Sakai, Hisato Kawakami, Takeshi Teramura, Yuta Onodera, Elizabeth Somers, Keiji Furuuchi, Toshimitsu Uenaka, Ryoji Kato, Kazuhiko Nakagawa

Clinical and translational medicine　11　(6)　e454　2021年6月
出版者・発行元： Wiley
DOI： 10.1002/ctm2.454 　

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BACKGROUND: The main function of folate receptor α (FOLRα) has been considered to mediate intracellular folate uptake and induce tumor cell proliferation. Given the broad spectrum of expression among malignant tumors, including gastric cancer (GC) but not in normal tissue, FOLRα represents an attractive target for tumor-selective drug delivery. However, the efficacy of anti-FOLRα monoclonal antibodies (mAbs) has not been proved so far, with the reason for this failure remaining unclear, raising the need for a better understanding of FOLRα function. METHODS: The distribution of FOLRα in GC cells was evaluated by immunohistochemistry. The impacts of FOLRα expression on the survival of GC patients and GC cell lines were examined with the Gene Expression Omnibus database and by siRNA of FOLRα. RNA-sequencing and Microarray analysis was conducted to identify the function of FOLRα. Proteins that interact with FOLRα were identified with shotgun LC-MS/MS. The antitumor efficacy of the anti-FOLRα mAb farletuzumab as well as the antibody-drug conjugate (ADC) consists of the farletuzumab and the tublin-depolymerizing agent eribulin (MORAb-202) was evaluated both in vitro and in vivo. RESULTS: FOLRα was detected both at the cell membrane and in the cytoplasm. Shorter overall survival was associated with FOLRα expression in GC patients, whereas reduction of FOLRα attenuated cell proliferation without inducing cell death in GC cell lines. Transcriptomic and proteomic examinations revealed that the FOLRα-expressing cancer cells possess a mechanism of chemotherapy resistance supported by MDM2, and FOLRα indirectly regulates it through a chaperone protein prohibitin2 (PHB2). Although reduction of FOLRα brought about vulnerability for oxaliplatin by diminishing MDM2 expression, farletuzumab did not suppress the MDM2-mediated chemoresistance and cell proliferation in GC cells. On the other hand, MORAb-202 showed significant antitumor efficacy. CONCLUSIONS: The ADC could be a more reasonable choice than mAb as a targeting agent for the FOLRα-expressing tumor.
An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability-High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7). 国際誌

Hisato Kawakami, Shuichi Hironaka, Taito Esaki, Kazuaki Chayama, Masahiro Tsuda, Naotoshi Sugimoto, Shigenori Kadowaki, Akitaka Makiyama, Nozomu Machida, Hidekazu Hirano, Kenro Hirata, Hiroki Hara, Hiroshi Yabusaki, Yoshito Komatsu, Kei Muro

Cancers　13　(4)　805-805　2021年2月15日
出版者・発行元： {MDPI} {AG}
DOI： 10.3390/cancers13040805 　

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Nivolumab (NIVO) plus low-dose ipilimumab (IPI) has shown a promising survival benefit in first-line treatment of microsatellite instability-high (MSI-H) colorectal cancer. We hypothesized that this regimen might also be beneficial for MSI-H gastric cancer (GC), which accounts for ~5% of all GC cases. NO LIMIT (WJOG13320G/CA209-7W7) is an investigator-initiated, single-arm, open-label, 14-center phase 2 trial of NIVO plus low-dose IPI for MSI-H GC in the first-line setting. Eligibility criteria include unresectable advanced, recurrent, or metastatic gastric or esophagogastric junction cancer with a histologically confirmed diagnosis of adenocarcinoma; confirmed MSI-H status with the MSI-IVD Kit (FALCO); no prior systemic anticancer therapy; an Eastern Cooperative Oncology Group performance status of 0 or 1; and a measurable lesion per RECIST 1.1. The primary objective of the study is to determine the overall response rate (ORR) for the NIVO+IPI regimen as assessed by blinded independent central review. Secondary end points include progression-free survival, overall survival, duration of response, safety, tolerability, and biomarkers. The number of patients was set at 28 on the basis of the threshold and expected ORR values of 35 and 65%, respectively, with a one-sided alpha error of 0.025 and power of 0.80. Subjects will receive treatment with nivolumab (240 mg) biweekly in combination with ipilimumab (1 mg/kg) every 6 weeks. The results of this study should clarify the therapeutic potential of NIVO+IPI for MSI-H GC in the first-line setting. Trial registration: JapicCTI-205400.
Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies. 国際誌

Yoshiaki Nakamura, Hiroya Taniguchi, Masafumi Ikeda, Hideaki Bando, Ken Kato, Chigusa Morizane, Taito Esaki, Yoshito Komatsu, Yasuyuki Kawamoto, Naoki Takahashi, Makoto Ueno, Yoshinori Kagawa, Tomohiro Nishina, Takeshi Kato, Yoshiyuki Yamamoto, Junji Furuse, Tadamichi Denda, Hisato Kawakami, Eiji Oki, Takako Nakajima, Naohiro Nishida, Kensei Yamaguchi, Hisateru Yasui, Masahiro Goto, Nobuhisa Matsuhashi, Koushiro Ohtsubo, Kentaro Yamazaki, Akihito Tsuji, Wataru Okamoto, Katsuya Tsuchihara, Takeharu Yamanaka, Izumi Miki, Yasutoshi Sakamoto, Hiroko Ichiki, Masayuki Hata, Riu Yamashita, Atsushi Ohtsu, Justin I Odegaard, Takayuki Yoshino

Nature medicine　26　(12)　1859-1864　2020年12月

DOI： 10.1038/s41591-020-1063-5 　

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Comprehensive genomic profiling enables genomic biomarker detection in advanced solid tumors. Here, to evaluate the utility of circulating tumor DNA (ctDNA) genotyping, we compare trial enrollment using ctDNA sequencing in 1,687 patients with advanced gastrointestinal (GI) cancer in SCRUM-Japan GOZILA (no. UMIN000016343), an observational ctDNA-based screening study, to enrollment using tumor tissue sequencing in the same centers and network (GI-SCREEN, 5,621 patients). ctDNA genotyping significantly shortened the screening duration (11 versus 33 days, P < 0.0001) and improved the trial enrollment rate (9.5 versus 4.1%, P < 0.0001) without compromising treatment efficacy compared to tissue genotyping. We also describe the clonal architecture of ctDNA profiles in ~2,000 patients with advanced GI cancer, which reinforces the relevance of many targetable oncogenic drivers and highlights multiple new drivers as candidates for clinical development. ctDNA genotyping has the potential to accelerate innovation in precision medicine and its delivery to individual patients.
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. 国際誌

Kohei Shitara, Yung-Jue Bang, Satoru Iwasa, Naotoshi Sugimoto, Min-Hee Ryu, Daisuke Sakai, Hyun-Cheol Chung, Hisato Kawakami, Hiroshi Yabusaki, Jeeyun Lee, Kaku Saito, Yoshinori Kawaguchi, Takahiro Kamio, Akihito Kojima, Masahiro Sugihara, Kensei Yamaguchi

The New England journal of medicine　382　(25)　2419-2430　2020年6月18日

DOI： 10.1056/NEJMoa2004413 　

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BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer. METHODS: In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab, were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy. The primary end point was the objective response, according to independent central review. Secondary end points included overall survival, response duration, progression-free survival, confirmed response (response persisting ≥4 weeks), and safety. RESULTS: Of 187 treated patients, 125 received trastuzumab deruxtecan and 62 chemotherapy (55 received irinotecan and 7 paclitaxel). An objective response was reported in 51% of the patients in the trastuzumab deruxtecan group, as compared with 14% of those in the physician's choice group (P<0.001). Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months; hazard ratio for death, 0.59; 95% confidence interval, 0.39 to 0.88; P = 0.01, which crossed the prespecified O'Brien-Fleming boundary [0.0202 on the basis of number of deaths]). The most common adverse events of grade 3 or higher were a decreased neutrophil count (in 51% of the trastuzumab deruxtecan group and 24% of the physician's choice group), anemia (38% and 23%, respectively), and decreased white-cell count (21% and 11%). A total of 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group; no drug-related deaths occurred in the physician's choice group. CONCLUSIONS: Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer. Myelosuppression and interstitial lung disease were the notable toxic effects. (Funded by Daiichi Sankyo; DESTINY-Gastric01 ClinicalTrials.gov number, NCT03329690.).
Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance. 国際誌

Seiichiro Mitani, Hisato Kawakami

Cancers　12　(2)　400-400　2020年2月10日
出版者・発行元： {MDPI} {AG}
DOI： 10.3390/cancers12020400 　

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Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody-drug conjugates that are under development and have shown promising antitumor activity in early studies.
[fam‐] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification 国際誌査読有り

Naoki Takegawa, Junji Tsurutani, Hisato Kawakami, Kimio Yonesaka, Ryoji Kato, Koji Haratani, Hidetoshi Hayashi, Masayuki Takeda, Yoshikane Nonagase, Osamu Maenishi, Kazuhiko Nakagawa

International Journal of Cancer　145　(12)　3414-3424　2019年5月
出版者・発行元： Wiley
DOI： 10.1002/ijc.32408 　
Study protocol of the C-SOLVE (JACCRO GC-12) trial; a randomized, non-comparative phase II trial of CapeOX or SOX plus zolbetuximab in HER2-negative, CLDN18.2-positive unresectable advanced gastric or esophagogastric junction cancer. 国際誌

Satoshi Yuki, Hisato Kawakami, Kazuaki Harada, Yohei Kubota, Kyongsun Pak, Yoshihiro Kakeji, Masanori Terashima, Eishi Baba, Kei Muro, Yu Sunakawa, Wataru Ichikawa, Masashi Fujii

BMC cancer　2026年7月17日

DOI： 10.1186/s12885-026-16478-1 　

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BACKGROUND: Capecitabine + oxaliplatin (CapeOX) + zolbetuximab and 5-FU + oxaliplatin (mFOLFOX6) + zolbetuximab are recommended as first-line treatments for chemotherapy-naïve patients with HER2-negative, CLDN18.2-positive advanced gastric or esophagogastric junction cancer. However, no prospective trials have evaluated the efficacy and safety of S-1 + oxaliplatin (SOX) + zolbetuximab. This study is planned as a non-comparative, prospective, randomized phase II clinical trial to evaluate the efficacy and safety of SOX + zolbetuximab in chemotherapy-naïve patients with HER2-negative, CLDN18.2-positive advanced gastric or esophagogastric junction cancer. METHODS/DESIGN: This randomized study will enroll patients ≥ 18 years old with histologically confirmed HER2-negative, CLDN18.2-positive (IHC defined as ≥ 75% of tumour cells showing moderate-to-strong membranous CLDN18 staining) advanced gastric or esophagogastric junction cancer. Participants (n = 140) will be randomly assigned (1:1) to receive either SOX + zolbetuximab or CapeOX + zolbetuximab. The primary endpoint is the 12-month progression-free survival (PFS) rate, with a threshold of 17% and an expected rate of 33% for SOX + zolbetuximab. To account for a 10% deviation risk, the target enrollment for each arm is 70 patients. CapeOX + zolbetuximab will serve as a prospective observational arm without hypothesis testing. Secondary endpoints will include PFS, overall survival, objective response rate, disease control rate, duration of response, time to response, and safety. The enrollment period is 2 years, followed by a 2-year observation period. DISCUSSION: Since replacing capecitabine with S-1 should provide the same level of therapeutic efficacy, SOX + zolbetuximab may be increasingly used to treat advanced gastric or esophagogastric junction cancer in Asian countries. Verifying the efficacy and safety of SOX + zolbetuximab is thus an important task. TRIAL REGISTRATION: The protocol has been registered at the website of the Japan Registry of Clinical Trials (JRCT), Japan (protocol ID jRCTs031240510, protocol version: 1.11) on November 26, 2024. The details are available at https://jrct.mhlw.go.jp/.
Clinical utility of comprehensive genomic profiling tests using MTB management system at a single center in Japan. 国際誌

Chie Sarudate, Miki Dobashi, Maako Kawamura, Hidekazu Shirota, Tomoyuki Iwasaki, Hiroshi Tada, Muneaki Shimada, Naoki Kawamorita, Masayuki Kanamori, Eisaku Miyauchi, Hidetaka Niizuma, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Keigo Komine, Masanobu Takahashi, Toru Furukawa, Aya Yokota, Eiji Kanamori, Hisato Kawakami, Chikashi Ishioka

Scientific reports　2026年7月7日

DOI： 10.1038/s41598-026-61124-2 　

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Cancer genomic medicine interprets genetic information for diagnosis and treatment. It requires an organized team of experts from various fields to discuss treatment recommendations at a molecular tumor board (MTB). It is also important to track patient outcomes based on these decisions and seamlessly incorporate them into future discussions at the MTB. We developed a system to manage the MTB efficiently. Using this system, we followed the outcome and prognosis of 1643 patients whose treatment was discussed at the MTB and evaluated the utility of a realistic comprehensive genomic profiling (CGP) test. Treatment recommendations were made for 240 patients (14% of the total cases). Of these, 118 (7% of the total) were treated with the drugs recommended by the MTB. The cancer type with the highest percentage of patients in which treatment recommendations were made and drugs were administered was thyroid cancer, followed by breast cancer, lung cancer, prostate cancer, and cholangiocarcinoma. While cancer-specific overall survival was inconclusive due to few cases, CGP-recommended treatment significantly extended patient survival from the CGP test date. This analysis, utilizing our patient follow-up system, suggests that CGP testing expands treatment options for a subset of patients and may improve treatment efficacy.
Association between antibiotic use, immune-related adverse events, and efficacy of immunotherapy in esophageal squamous cell carcinoma.

Tomoaki Shirakawa, Hiroo Imai, Ken Saijo, Ryo Saito, Shiori Ishikawa, Iori Takahashi, Keigo Komine, Kota Ouchi, Yuki Kasahara, Sakura Taniguchi, Yuya Yoshida, Ryunosuke Numakura, Shonosuke Wakayama, Hidekazu Shirota, Masanobu Takahashi, Hisato Kawakami

International journal of clinical oncology　31　(7)　1258-1266　2026年7月

DOI： 10.1007/s10147-026-03036-9 　

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INTRODUCTION: Immune checkpoint inhibitors (ICIs) are essential for treating esophageal squamous cell carcinoma (ESCC). As antibiotics (Abx) may reduce ICI efficacy, and immune-related adverse events (irAEs) relate to better outcomes, we investigated their association. PATIENTS AND METHODS: We retrospectively analyzed 121 advanced or metastatic ESCC patients treated with ICIs, assessing outcomes based on Abx use and irAEs. RESULTS: Forty-one patients (33.9%) were in the Abx (+) group, showing a significantly shorter median progression-free survival (PFS) (2.5 vs. 6.5 months; p = 0.029) and lower disease control rate (36.8% vs. 60.9%; p = 0.0145) than those in the Abx (-) group. irAEs were less frequent in the Abx (+) group (29.3% vs. 58.8%; p = 0.0037). The positive impact of irAEs on ICI efficacy was significant in overall population [irAE(-) vs. irAE(+): PFS, 4.4 months (95% CI 2.5-5.3) vs. 8.8 months (95% CI 5.9-13.7); log-rank p = 0.001; Hazard ratio (HR) 1.76, 95% CI 1.14-2.74; p = 0.011; overall survival (OS), 10.6 months (95% CI 7.0-13.1) vs. 18.1 months (95% CI 9.2-25.9); log-rank p = 0.043; HR 1.61, 95% CI 1.01-2.55; p = 0.046] but diminished if received Abx. Notably, the Abx (-)/irAE (+) group had the best outcomes, while the Abx (+)/irAE (-) group had the worst PFS (8.7 vs. 2.4 months; HR 2.07; p = 0.011) and OS (18.1 and 6.8 months; HR 1.89; p = 0.036). CONCLUSION: Antibiotic use was linked to reduced ICI efficacy and fewer irAEs, suggesting impaired immune activation in ESCC patients.
Coexistence of TP53 and KRAS mutations identifies a molecular subset of biliary tract cancer with poor overall survival after first-line immunochemotherapy 国際誌

Shiori Ishikawa, Kota Ouchi, Shonosuke Wakayama, Shunsuke Oyamada, Tomoyuki Iwasaki, Ryunosuke Numakura, Yuya Yoshida, Sakura Taniguchi, Yuki Kasahara, Keigo Komine, Ken Saijo, Hidekazu Shirota, Hisato Kawakami

European Journal of Cancer　242　116826-116826　2026年6月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.ejca.2026.116826 　

ISSN：0959-8049

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BACKGROUND: Biliary tract cancer (BTC) is a biologically heterogeneous malignancy with a poor prognosis. Although the combination of an immune checkpoint inhibitor (ICI) with gemcitabine plus cisplatin (GC) is now a standard first-line therapy for advanced BTC, the genomic determinants of treatment outcome have remained unclear. METHODS: We investigated the relation between genomic alterations and overall survival (OS) in BTC patients treated with first-line GC or GC + ICI using data from the Japanese Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. RESULTS: Among 1875 BTC patients with available OS data, genomic alterations of TP53 (53.3%), CDKN2A (25.4%), and KRAS (21.0%) were the most frequently identified and were significantly associated with inferior OS in both GC and GC + ICI groups. TP53 and KRAS mutations showed numerically higher hazard ratios (HRs) in the GC + ICI group than in the GC group (HR of 1.53 [95% confidence interval (CI), 1.25-1.88] vs. 1.29 [95% CI, 1.03-1.61] for TP53; HR of 1.78 [95% CI, 1.45-2.17] vs. 1.40 [95% CI, 1.07-1.83] for KRAS), whereas CDKN2A alterations showed similar effects across treatments. The TP53/KRAS double-mutant subgroup showed the poorest survival outcome, with shorter median OS on GC + ICI than on GC (11.8 vs. 15.9 months; HR, 1.47 [95% CI, 0.99-2.18]), although no significant interaction between treatment and double-mutant status was observed (interaction P = 0.1655). CONCLUSION: TP53 and KRAS co-mutation may identify a molecular subset of BTC with poor prognosis in the context of GC + ICI.
Impact of prior immune checkpoint inhibitor on trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory analysis of the EN-DEAVOR study. 国際誌

Yukiya Narita, Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Naotoshi Sugimoto, Hirotaka Konishi, Satoshi Morita, Keiko Minashi, Motohiro Imano, Rin Inamoto, Tomohiro Nishina, Takeshi Kawakami, Motohisa Hagiwara, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro

Japanese journal of clinical oncology　56　(5)　538-545　2026年5月7日

DOI： 10.1093/jjco/hyaf216 　

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BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) presents significant therapeutic challenges due to its molecular heterogeneity. Previous studies suggest that immune checkpoint inhibitors (ICIs) may enhance the efficacy of subsequent HER2-targeted therapy. However, evidence suggesting an optimal sequence for nivolumab and trastuzumab deruxtecan (T-DXd) treatment is limited. This exploratory analysis of EN-DEAVOR evaluated the effectiveness and safety of administering T-DXd relative to the timing of prior ICI administration. METHODS: This study assessed real-world outcomes of T-DXd in patients with HER2-positive AGC stratified by prior ICI exposure: within 2 months of nivolumab (Group A), >2 months (Group B), and no prior nivolumab (Group C). The primary effectiveness endpoints included real-world progression-free survival (rwPFS) and objective response rate (ORR). Safety endpoints included grade ≥ 3 adverse events (AEs). RESULTS: Among 311 eligible patients, Group A showed the longest median rwPFS (n = 63; 6.9 months) compared with Group B (n = 63; 4.6 months) and Group C (n = 185; 4.2 months). The risk of progression was significantly lower in Group A compared with Group B (hazard ratio [95% confidence interval]: 0.6 [0.4-0.9]; P = .0074). ORR was numerically highest in Group A (54.9%) versus Group B (30.8%) and Group C (43.4%). More patients in Group B (58.7%) experienced grade ≥ 3 AEs than in Group A (50.8%) and Group C (43.8%). No new safety signals were observed. CONCLUSIONS: Initiating T-DXd within 2 months post-ICI may enhance therapeutic efficacy in HER2-positive AGC without affecting safety, supporting a potential sequencing option after ICI therapy.
Metabolic and functional pathways of gut microbiota in patients with gastric cancer. 国際誌

Ryo Matoba, Hiroshi Iijima, Yasuhiro Sakamoto, Ryohei Kawabata, Atsushi Ishiguro, Yusuke Akamaru, Yosuke Kito, Masaki Aizawa, Jin Matsuyama, Masazumi Takahashi, Akitaka Makiyama, Takahisa Suzuki, Masahiro Tsuda, Hisateru Yasui, Jun Hihara, Hiroyuki Okuda, Junji Kawada, Takashi Yoshioka, Hisato Kawakami, Takako Eguchi Nakajima, Kei Muro, Wataru Ichikawa, Masashi Fujii, Yu Sunakawa

Scientific reports　16　(1)　2026年4月10日

DOI： 10.1038/s41598-026-47830-x 　

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We analysed the differences in bacterial composition between 475 Japanese patients with advanced gastric cancer (median age, 70 years; median BMI 20.0) and 106 healthy individuals using a comprehensive metagenome shotgun analysis. Among the patients with advanced gastric cancer, 71% were male, 37% had relapsed, and 55.5% previously underwent gastrectomy. Bifidobacterium, Anaerostipes, and Parabacteroides were predominant in healthy individuals, whereas Streptococcus, Lactobacillus, and Odoribacter were predominant in patients with advanced gastric cancer. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that butanoate and pyruvate metabolism was enriched in healthy individuals, whereas factors, such as ABC transporters and ribosomes, were enriched in patients with advanced gastric cancer. Cluster analysis broadly classified patients with advanced gastric cancer and healthy individuals into two clusters; however, clustering using pathway data more clearly classified patients with advanced gastric cancer and healthy individuals than clustering using flora analysis. Moreover, healthy individuals showed higher bacterial flora diversity than those with advanced gastric cancer. Although the dataset we used was limited and may be difficult to generalise, we identified some molecular characteristics and functional pathways of the microbial genera within the intestines of patients with advanced gastric cancer.
Real-world sequential treatment patterns and outcomes in the new era of immunotherapy for advanced gastric cancer in Japan. 国際誌

Hisato Kawakami, Yoshinori Tanizawa, Tetsu Shimizu

Future oncology (London, England)　22　(8)　969-980　2026年4月

DOI： 10.1080/14796694.2026.2642222 　

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BACKGROUND: We investigated treatment patterns and outcomes in patients with advanced gastric cancer (AGC) after nivolumab first-line therapy approval in Japan in 2021. METHODS: This retrospective study used data from the Medical Data Vision database. Treatment patterns were described. Overall time-to-treatment discontinuation (TTD) from the start of each line was estimated. RESULTS: Among 11,276 included patients, 1589 received anti-HER2+chemotherapy (Cx) at any line and regarded as HER2-positive AGC (anti-HER2+Cx group). Among the other, 9687 who presumably had HER2-negative AGC, 5722 received nivolumab+Cx at first-line (Nivo+Cx group), and 3965 received Cx alone at first-line (Cx group). Nivolumab+S-1+oxaliplatin (4,104/11,276; 36.4%) was the most common first-line regimen. The most common second-line and third-line regimens were ramucirumab+paclitaxel (PTX) (or NabPTX) (3092/4345; 71.2%) and nivolumab (490/1712; 28.6%). Median overall TTD from start of first-line therapy was 13.3, 10.5, and 6.8 months in anti-HER2+Cx, Nivo+Cx, and Cx groups. Median overall TTD from start of second-line therapy was 6.2, 3.5, and 4.9 months with ramucirumab combination therapy, ramucirumab monotherapy, and other therapies. CONCLUSIONS: After first-line nivolumab was introduced for AGC in Japan, treatment patterns remained consistent with Japanese Gastric Cancer Association guidelines. Optimizing sequential therapy, including nivolumab at first-line and ramucirumab combination at second-line, may improve outcomes.
Inverse Relation Between Responses to Pembrolizumab Plus Chemotherapy and Subsequent Cetuximab Plus Paclitaxel in Head and Neck Cancer: Role of the Janus Kinase-Signal Transducer and Activator of Transcription Signaling Pathway. 国際誌

Ken Saijo, Hiroo Imai, Tomoyuki Iwasaki, Ryo Ishii, Kenjiro Higashi, Akira Ohkoshi, Yuto Yamazaki, Tomoaki Shirakawa, Ryo Saito, Shonosuke Wakayama, Ryunosuke Numakura, Yuya Yoshida, Sakura Taniguchi, Yuki Kasahara, Kota Ouchi, Keigo Komine, Hidekazu Shirota, Masanobu Takahashi, Takashi Suzuki, Yukio Katori, Chikashi Ishioka, Hisato Kawakami

JCO precision oncology　10　(4)　e2501050　2026年4月

DOI： 10.1200/PO-25-01050 　

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PURPOSE: Cetuximab plus paclitaxel (CET + PTX) is frequently administered after immune checkpoint inhibitor (ICI) therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, the relation between responses to these two treatment lines has remained unclear. We aimed to clarify this relation and its potential mechanisms, focusing on the patients treated with pembrolizumab plus chemotherapy and subsequent CET + PTX. PATIENTS AND METHODS: We retrospectively reviewed patients with R/M-HNSCC who received pembrolizumab plus chemotherapy and subsequent CET + PTX at Tohoku University Hospital between April 2020 and November 2025. Clinical outcomes of CET + PTX were assessed according to response to prior pembrolizumab plus chemotherapy. Gene expression and immunohistochemical (IHC) analyses of pretreatment tumor samples, as well as HNSCC cell-based assays, were performed. RESULTS: This study included 30 patients. The overall response rate (ORR) to subsequent CET + PTX was 57%. The ORR and progression-free survival (PFS) of CET + PTX were significantly greater in patients who showed progressive disease on pembrolizumab plus chemotherapy than in responders (P < .01). Gene expression analyses revealed enrichment of Janus kinase (JAK)-STAT signaling pathways in pembrolizumab plus chemotherapy nonresponders who responded to CET + PTX. Consistently, high tumor expression of phosphorylated STAT3 was observed exclusively in this subgroup by IHC. CET sensitivity across HNSCC cell lines correlated with STAT3 phosphorylation. CONCLUSION: Responses to pembrolizumab plus chemotherapy and subsequent CET + PTX were inversely associated in R/M-HNSCC. Activation of the JAK-STAT signaling pathway, particularly STAT3 phosphorylation, may identify tumors resistant to pembrolizumab plus chemotherapy but sensitive to CET + PTX, thereby guiding post-ICI treatment selection.
Randomized phase II study of FOLFIRI plus ramucirumab versus FOLFOXIRI plus ramucirumab as first-line treatment for metastatic colorectal cancer: WJOG9216G (RECAST). 国際誌

Yosuke Kito, Kentaro Yamazaki, Hirokazu Shoji, Takeshi Yamada, Takahiro Tsushima, Seiichiro Mitani, Kazuhiro Shiraishi, Hisateru Yasui, Hiroki Hara, Kenro Hirata, Taito Esaki, Yudai Shinohara, Takao Tsuzuki, Shinya Kajiura, Toshiki Masuishi, Naoki Izawa, Eishi Baba, Kohei Murata, Naoya Akazawa, Yozo Suzuki, Hironaga Satake, Narikazu Boku, Ichinosuke Hyodo, Kenichi Yoshimura, Hisato Kawakami, Shuichi Hironaka, Kei Muro

European journal of cancer (Oxford, England : 1990)　238　116688-116688　2026年3月19日

DOI： 10.1016/j.ejca.2026.116688 　

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BACKGROUND: FOLFOXIRI plus bevacizumab improved efficacies and increased some adverse events in untreated metastatic colorectal cancer (mCRC), compared with the doublet plus bevacizumab. The clinical outcomes of ramucirumab (RAM) in combination with FOLFIRI or FOLFOXIRI as a first-line treatment are unknown. In this randomized phase II study (WJOG9216G), we compared the efficacy and safety of these regimens to determine which is more promising. METHODS: Patients with untreated mCRC were randomly assigned to the FOLFIRI-RAM or FOLFOXIRI-RAM arms. The primary endpoint was a confirmed objective response rate (ORR), and secondary endpoints included early tumor shrinkage (ETS), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: In total, 122 patients were randomized. The confirmed ORR was 59.3% and 60.3% in the FOLFIRI-RAM and FOLFOXIRI-RAM arms, respectively (odds ratio 1.04; P = 0.91). With a median follow-up period of 42.1 and 40.4 months, PFS was comparable between the FOLFIRI-RAM and FOLFOXIRI-RAM arms (median, 11.5 and 10.5 months). ETS rate (71.2% and 52.4%) and OS (median, 32.6 and 28.2 months) were significantly better in the FOLFIRI-RAM arm than in the FOLFOXIRI-RAM arm. The major grade ≥ 3 adverse events in the FOLFIRI-RAM and FOLFOXIRI-RAM arms were neutropenia (44.1% and 72.6%), anorexia (3.4% and 14.5%), and febrile neutropenia (3.4% and 11.3%). CONCLUSIONS: FOLFOXIRI plus RAM was not superior to FOLFIRI plus RAM in terms of efficacy, including ORR, in patients with untreated mCRC. Instead, first-line FOLFIRI plus RAM showed clinical efficacy and safety profiles comparable to those of doublet chemotherapy plus bevacizumab.
Comparative study of the short-term outcomes of gastric cancer surgery between Japanese Gastric cancer association-certified and non-certified institutions: a retrospective cohort analysis using a national database in Japan.

Tomoyuki Matsunaga, Hideki Endo, Hiroyuki Yamamoto, Koshi Kumagai, Shingo Kanaji, Hisato Kawakami, Chika Kusano, Ryoji Kushima, Mitsuhiro Fujishiro, Kensei Yamaguchi, Takaki Yoshikawa, Yuichiro Doki, Yoshihiro Kakeji, Yoshiyuki Fujiwara

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　29　(2)　415-423　2026年3月

DOI： 10.1007/s10120-025-01694-8 　

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BACKGROUND: This study assessed the impact of an institutional certification system that was newly introduced by the Japanese Gastric Cancer Association on short-term surgical outcomes in patients with gastric cancer using data from the National Clinical Database. METHODS: A retrospective cohort study of distal gastrectomy and total gastrectomy procedures performed between January 2020 and December 2022 was conducted. The institutions were classified into three categories: type A, type B, and non-certified institutions, in decreasing order of certification stringency. The primary outcome was the incidence of grade ≥ IIIa postoperative complications based on the Clavien-Dindo classification system. The secondary outcome was surgery-related mortality. Logistic regression with risk adjustment, estimated using generalized estimating equations, was used to account for intra-cluster correlation. RESULTS: There was no significant difference in the risks of distal gastrectomy-related complications across the three institution types. However, type A- (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.31-0.49) and type B-certified institutions (OR 0.59, 95% CI 0.49-0.71) had a significantly lower mortality risk than non-certified ones. On the other hand, Type A- (OR 1.25, 95% CI 1.09-1.44) and type B-certified institutions (OR 1.17, 95% CI 1.03-1.33) had higher risks of postoperative total gastrectomy-related complications than non-certified ones. Nevertheless, type A- (OR 0.41, 95% CI 0.29-0.58) and type B-certified institutions (OR 0.67, 95% CI 0.51-0.88) had significantly lower surgery-related mortality risks than non-certified ones. CONCLUSIONS: Certified institutions demonstrated lower surgical mortality risks, highlighting the benefits of the certification system and the importance of institutional quality.
Attenuated Li–Fraumeni syndrome with TP53 p.R181H in a Japanese patient with metastatic rectal adenocarcinoma: a case report 国際誌

Yuki Kasahara, Masanobu Takahashi, Yoshifumi Kawamura, Yoko Aoki, Tetsuya Niihori, Maako Kawamura, Shinnosuke Yamamoto, Hidekazu Shirota, Ken Saijo, Hiroo Imai, Keigo Komine, Kota Ouchi, Sakura Taniguchi, Yuya Yoshida, Ryunosuke Numakura, Shiori Ishikawa, Tomoaki Shirakawa, Ryo Saito, Chikashi Ishioka, Hisato Kawakami

Familial Cancer　25　(1)　18-18　2026年2月3日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1007/s10689-026-00529-4 　

eISSN：1573-7292

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Li-Fraumeni syndrome (LFS) is a hereditary cancer-predisposing disorder caused by germline pathogenic variants in the TP53 gene. Attenuated LFS represents a clinically milder form characterized by lower penetrance and later tumor onset, evading standard diagnostic criteria. We report a case of a 36-year-old Japanese woman who presented with hematochezia and was diagnosed with metastatic rectal adenocarcinoma. After failure of the first- to third-line chemotherapies, plasma-based comprehensive genomic profiling (CGP) was performed. The assay revealed a TP53 p.R181H variant (allele frequency: 0.512), KRAS p.G12D variant, PIK3CA p.E545K variant, and a CTNNB1 splicing variant. Family history included multiple gastrointestinal and hematological malignancies in first- and second-degree relatives. Germline testing confirmed heterozygosity of TP53 p.R181H, a temperature-sensitive variant suggested to have reduced penetrance. Notably, this variant is relatively common in European populations but rare in East Asian cohorts. To the best of our knowledge, this is the first reported East Asian case of attenuated LFS associated with the TP53 p.R181H variant. This case underscores the broader phenotypic spectrum of LFS. With the growing use of CGP, LFS may be identified more frequently in East Asia, potentially revealing attenuated LFS missed by traditional diagnostic criteria.
Solvent-based or nab-paclitaxel plus ramucirumab for pretreated gastric cancer with peritoneal dissemination and prespecified biomarker analysis (P-SELECT/WJOG10617G): a randomised phase 2 trial in Japan 国際誌

Kenro Hirata, Yasuo Hamamoto, Hirokazu Shoji, Hiroki Hara, Chihiro Kondoh, Hisateru Yasui, Takeshi Kajiwara, Eishi Baba, Takayuki Ando, Naotoshi Sugimoto, Hisato Kawakami, Hiroo Katsuya, Michitaka Nagase, Yoshiyuki Yamamoto, Kenichi Yoshimura, Masahiko Ando, Chiyo K. Imamura, Kentaro Yamazaki, Shuichi Hironaka, Kei Muro

eClinicalMedicine　92　103768-103768　2026年2月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.eclinm.2026.103768 　

ISSN：2589-5370

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BACKGROUND: Gastric cancer (GC) with peritoneal dissemination remains a challenge with poor prognosis and limited treatment options. We aimed to compare solvent-based paclitaxel (sb-PTX) + ramucirumab (RAM) vs. nanoparticle-albumin-bound paclitaxel (nab-PTX) + RAM as second-line therapy for unresectable or recurrent GC with peritoneal dissemination. METHODS: This prospective, randomised, open-label, multicentre phase 2 trial was conducted at 58 centres within the West Japan Oncology Group (WJOG) in Japan. Eligible participants were patients with histologically-confirmed GC with peritoneal dissemination refractory or intolerant to first-line therapy. Patients were randomised 1:1 to receive sb-PTX + RAM or nab-PTX + RAM. Primary endpoint was overall survival (OS); key secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), safety, and protocol-specified biomarker analyses including the assessment of stromal caveolin-1 (Cav-1) expression by immunohistochemistry on archival tumour specimens. The data cutoff for the analysis presented herein was January 27, 2021. This trial was registered in the Japan Registry of Clinical Trials (jRCTs031180022). FINDINGS: Between Oct 1, 2018, and Jan 27, 2020, 105 patients were assigned to sb-PTX + RAM (n = 53) or nab-PTX + RAM (n = 52). Median follow-up was 18.1 months. Median OS was 8.1 months with sb-PTX + RAM and 7.2 months with nab-PTX + RAM (HR [nab-PTX + RAM vs. sb-PTX + RAM], 0.960; 95% CI, 0.621-1.484; P = 0.631). Median PFS was 5.1 vs. 3.9 months (HR [nab-PTX + RAM vs. sb-PTX + RAM], 0.965; 95% CI, 0.642-1.450; P = 0.893). ORR was 20.7% vs. 20.0% (P = 0.993), and DCR was 77.4% vs. 63.5% (P = 0.150), with sb-PTX + RAM and nab-PTX + RAM. Grade≥3 neuropathy occurred in 7.5% with sb-PTX + RAM and 17.6% with nab-PTX + RAM, and febrile neutropenia in 11.3% vs. 5.9%. In biomarker analysis, OS and PFS improved stepwise with increasing Cav-1 expression in patients receiving nab-PTX + RAM (P = 0.007, P = 0.012); no such association was observed with sb-PTX + RAM. Among patients with high stromal Cav-1 expression (IHC score 3+), nab-PTX + RAM showed some evidence of improved OS compared with sb-PTX + RAM (HR [nab-PTX + RAM vs. sb-PTX + RAM], 0.371; 95% CI, 0.130-1.060; P = 0.055). The interaction between Cav-1 expression and treatment arm showed a non-significant trend (HR for interaction, 0.364; 95% CI, 0.115-1.152; P = 0.086), consistent with this finding. INTERPRETATION: Treatment with nab-PTX + RAM did not meet the prespecified threshold (HR < 0.90) for promising efficacy in patients with GC and peritoneal dissemination. High stromal Cav-1 expression was associated with improved efficacy of nab-PTX + RAM. Future studies should prospectively validate the predictive value of stromal Cav-1 in patients receiving nab-PTX + RAM. FUNDING: Taiho Pharmaceutical Co. Ltd.
Clinical Impact of Trastuzumab Deruxtecan in Patients With HER2-Positive Advanced Gastric Cancer and Ascites: Findings From the EN-DEAVOR Study

Keiko Minashi, Rin Inamoto, Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Naotoshi Sugimoto, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Motohiro Imano, Tomohiro Nishina, Takeshi Kawakami, Motohisa Hagiwara, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro

Journal of Gastric Cancer　2026年

DOI： 10.5230/jgc.2026.26.e42 　
Case Report: mTOR inhibitor treatment for epithelioid angiomyolipoma harboring biallelic TSC2 mutations. 国際誌

Shiori Ishikawa, Kota Ouchi, Shonosuke Wakayama, Yuki Kasahara, Keigo Komine, Hiroo Imai, Ken Saijo, Yuto Yamazaki, Masanobu Takahashi, Hidekazu Shirota, Hisato Kawakami

Frontiers in oncology　16　1735690-1735690　2026年

DOI： 10.3389/fonc.2026.1735690 　

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INTRODUCTION: Angiomyolipoma (AML) is a mesenchymal tumor composed of blood vessels, smooth muscle, and adipose tissue, and is generally considered benign. However, epithelioid angiomyolipoma (eAML) is a rare and aggressive variant with metastatic potential. Molecular characterization utilizing the tuberous sclerosis complex (TSC)-mTOR pathway is beneficial in advanced disease. This report describes the clinical course, histopathological findings, and molecular analysis of a patient with metastatic eAML. METHODS: A 59-year-old Japanese man with no personal or family history of tuberous sclerosis (TSC) was admitted to the hospital with gradually worsening back pain and initially diagnosed with clear cell renal cell carcinoma (ccRCC). He underwent nephrectomy, followed by hepatic recurrence treated with pazopanib and subsequent axitinib. Both were discontinued due to intolerance, and the two remaining liver metastases were surgically resected. Histopathological examination of the resected lesions revealed eAML. After several recurrences and resections, unresectable hepatic and pulmonary metastases eventually developed. RESULTS: Comprehensive genomic profiling (CGP) using the resected liver metastasis specimen identified two somatic TSC2 mutations: a frameshift mutation (p. P677fs*21; variant allele frequency [VAF] 0.0789) and a nonsense mutation (p. S1469*; VAF 0.0736), suggesting biallelic loss of TSC2. Based on these findings, everolimus, a mammalian/mechanistic target of rapamycin (mTOR) inhibitor, was recommended, which markedly reduced the size of the metastatic lesions and was continued for 24 months until disease progression without severe adverse events. DISCUSSION: This case suggests that CGP can help identify actionable alterations in eAML, such as TSC2 mutations, to guide personalized therapy with mTOR inhibitors.
Emergence of PALB2 Reversion Mutations as a Mechanism of Resistance to Niraparib in Breast Cancer: A Case Report. 国際誌

Maako Kawamura, Hiroshi Tada, Hidekazu Shirota, Miki Dobashi, Noriko Takenaga, Hiroyuki Yasojima, Narumi Harada-Shoji, Keigo Komine, Kenichi Nakamura, Minoru Miyashita, Hisato Kawakami

Cancer science　116　(12)　3540-3544　2025年12月

DOI： 10.1111/cas.70210 　

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This case study describes the clinical course of a 39-year-old woman with metastatic breast cancer harboring a germline PALB2 mutation who was treated with a PARP inhibitor. She initially demonstrated a clinical benefit with reduced tumor markers and favorable imaging findings. However, disease progression occurred after eight months. Liquid biopsy-based genomic profiling identified three PALB2 reversion mutations that restored homologous recombination, leading to treatment resistance. The case illustrates both the therapeutic potential of PARP inhibitors in PALB2-mutated cancers and the emergence of resistance. It emphasizes the importance of liquid biopsy-based genomic profiling for understanding tumor evolution and guiding treatment strategies.
Real-world evaluation of interstitial lung disease/pneumonitis in patients treated with trastuzumab deruxtecan for HER2-positive advanced or recurrent gastric cancer: a postmarketing surveillance study in Japan

H. Kawakami, K. Uchino, W. Hashimoto, K. Muro

ESMO Open　2025年12月

DOI： 10.1016/j.esmoop.2025.105914 　
Figure S1 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701609 　
Figure S3 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701603 　
Figure S4 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701600 　
Figure S2 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701606 　
Figure S5 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701597 　
Figure S7 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701591 　
Figure S8 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701588 　
Table S1 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701585 　
Figure S6 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701594 　
Table S2 from HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

2025年11月24日

DOI： 10.1158/1078-0432.30701582 　
Entrapment of a Guidewire Caused by the Chiari Network During Implantation of a Central Venous Port: A Case Report.

Shonosuke Wakayama, Rika Saito, Kota Ouchi, Yuya Yoshida, Hiromitsu Tannai, Hirofumi Watanabe, Shuto Kodera, Tomoyuki Iwasaki, Yoshifumi Kawamura, Masanobu Takahashi, Chikashi Ishioka, Hisato Kawakami

Internal medicine (Tokyo, Japan)　65　(12)　1632-1636　2025年11月6日

DOI： 10.2169/internalmedicine.6256-25 　

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A central venous (CV) port is an important device for cancer treatment, as it enables safe venous access. We herein report the case of an 82-year-old man with recurrent gastric cancer who experienced J-tip spring guidewire entrapment caused by the Chiari network during CV port implantation. The guidewire was pulled away, with a piece of tissue at its tip. The tissue comprised cardiomyocytes, stratified collagenous fibers, and elastic fibers. The condition was diagnosed as a Chiari network. Based on our experience, operators should be aware of the risk of Chiari network involvement even with a normal transthoracic echocardiogram result.
Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2024 for the treatment of colorectal cancer

Yusuke Kinugasa, Kay Uehara, Kensei Yamaguchi, Yutaka Saito, Keiko Murofushi, Tamotsu Sugai, Megumi Ishiguro, Soichiro Ishihara, Hideki Ueno, Shiro Oka, Takeshi Kato, Yukihide Kanemitsu, Hisato Kawakami, Hirotoshi Kobayashi, Yoshihiro Sakamoto, Manabu Shiozawa, Akio Shiomi, Eiji Shinozaki, Hirotoshi Takiyama, Hiroya Taniguchi, Takako Eguchi Nakajima, Kinichi Hotta, Keiji Matsuda, Kohei Murata, Satoshi Morita, Kentaro Yamazaki, Masahiro Yoshida, Naohiko Yamaguchi, Hiroyasu Kagawa, Shinichi Yamauchi, Yoichi Ajioka

International Journal of Clinical Oncology　30　(12)　2410-2463　2025年11月4日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1007/s10147-025-02899-8 　

ISSN：1341-9625

eISSN：1437-7772

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Abstract The number of deaths from colorectal cancer in Japan continues to rise, with over 50,000 deaths recorded in 2018. In the 2024 edition, revisions to all aspects of treatment were undertaken, with corrections and additions made based on knowledge gained since the 2022 version (drug therapy) and the 2019 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2024 for the treatment of colorectal cancer have been prepared to present standard treatment strategies, reduce disparities among institutions, avoid both unnecessary and insufficient treatment, and enhance mutual understanding between healthcare professionals and patients by making these guidelines accessible to the public. These guidelines were developed through consensus by the JSCCR Guideline Committee, following a careful review of evidence retrieved from literature searches and considering the medical insurance system and actual clinical practice in Japan. Therefore, these guidelines serve as a tool for managing colorectal cancer in real-world clinical settings. More specifically, they can be used to support obtaining informed consent from patients and selecting the most appropriate treatment method for each patient. Controversial topics were selected as clinical questions, and recommendations were provided. Each recommendation is accompanied by an evidence classification and a recommendation category, both based on consensus reached by the Guideline Committee members. This article presents the English version of the JSCCR guidelines 2024.
Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer: a FRESCO-2 subgroup analysis of patients enrolled in Japan.

Daisuke Kotani, Takayuki Yoshino, Toshiki Masuishi, Yu Sunakawa, Atsuo Takashima, Kentaro Yamazaki, Hisato Kawakami, Tomohiro Nishina, Yoshito Komatsu, Taito Esaki, Cathy Eng, Stacey Ukrainskyj, Rajash Pallai, Shivani Nanda, Zhao Yang, William Schelman, Marek Kania, Taroh Satoh

International journal of clinical oncology　30　(10)　2043-2052　2025年10月

DOI： 10.1007/s10147-025-02852-9 　

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BACKGROUND: In the phase 3 FRESCO-2 study, fruquintinib plus best supportive care (BSC) significantly improved overall survival (OS) versus placebo plus BSC in patients with refractory metastatic colorectal cancer (mCRC). We present the results of a FRESCO-2 post hoc subgroup analysis evaluating outcomes of patients enrolled in Japan. METHODS: In FRESCO-2, patients had previously received all standard chemotherapies, anti-VEGF and anti-EGFR therapies if indicated, and had progressed on, or were intolerant to trifluridine-tipiracil and/or regorafenib. Patients were randomized 2:1 to receive fruquintinib 5 mg or matching placebo by mouth once daily on days 1-21 in 28-day cycles, plus BSC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and safety. RESULTS: Of the 56 patients enrolled in Japan, 40 (71.4%) and 16 (28.6%) were randomized to fruquintinib and placebo, respectively. OS was improved with fruquintinib versus placebo (median 6.9 vs. 5.6 months; hazard ratio [HR], 0.42; 95% confidence interval [CI] 0.19 - 0.92). PFS was also improved with fruquintinib versus placebo (median 3.6 vs. 1.8 months; HR, 0.27; 95% CI 0.13 - 0.56). The incidence of grade ≥ 3 treatment-emergent adverse events (TEAEs) with fruquintinib versus placebo was 71.8% versus 29.4%; the most common grade ≥ 3 TEAEs with fruquintinib were hypertension (23.1%) and palmar-plantar erythrodysesthesia (17.9%). CONCLUSIONS: Fruquintinib improved OS and PFS versus placebo in FRESCO-2 patients enrolled in Japan and demonstrated a manageable safety profile. Results from the Japan subgroup were consistent with the global FRESCO-2 population, thus supporting fruquintinib as a novel treatment option for patients in Japan with refractory mCRC. CLINICAL TRIAL DETAILS: ClinicalTrials.gov; NCT04322539.
A placebo-controlled study of the doses and efficacy of Lentinula edodes mycelia for oxaliplatin-induced peripheral neuropathy in colorectal cancer 国際誌

Shogen Boku, Hironaga Satake, Seiichiro Mitani, Kiyoshi Maeda, Toshihiro Kudo, Toshifumi Yamaguchi, Tatsuya Takagi, Hisato Kawakami

Frontiers in Oncology　15　1577848-1577848　2025年8月11日
出版者・発行元： Frontiers Media SA
DOI： 10.3389/fonc.2025.1577848 　

eISSN：2234-943X

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Introduction Preclinical studies have demonstrated the potential of Lentinula edodes mycelium (L.E.M.) extract for managing oxaliplatin-induced peripheral neuropathy (OIPN). The efficacy and optimal dosage of L.E.M. for OIPN remain uncertain. We evaluated the efficacy and safety as well as the optimal dosage of L.E.M. extract for OIPN in patients with colorectal cancer (CRC). Methods After curative resection, we used a 1:1:1 ratio to randomly assign patients with CRC with persistent OIPN (defined by a visual analogue scale [VAS] numbness score ≥40 mm) to the low-dose (L.E.M. 300 mg twice daily [bid]), high-dose (L.E.M. 900 mg bid), and placebo groups. The primary endpoint of this double-blind, placebo-controlled phase 2 trial was the reduction in the VAS numbness score in the low-dose group compared with that in the placebo group at 12 weeks. Adverse events (AEs) and quality of life were evaluated. Results Forty-five patients were randomly assigned to the placebo (n = 15), low-dose (n = 15), and high-dose (n = 15) groups. At 12 weeks, no significant difference in the reduction of the VAS numbness score was observed when the low-dose and placebo groups were compared (−12.20 [95% confidence interval {CI}; −34.54 to 10.14] vs. −10.69 [95% CI; −27.07 to 5.69]; p = 0.83); however, the high-dose group showed a favorable trend compared with the placebo group (−12.20 vs. −29.32 [95% CI; −53.4 to −5.2]; p = 0.06). Grade 3 or higher AEs related to the intervention were not observed. Discussion High-dose L.E.M. extract resulted in a clinically meaningful improvement in VAS numbness scores without severe toxicity. Clinical Trial Registration https://jrct.mhlw.go.jp/en-latest-detail/jRCTs051210085, identifier jRCTs051210085.
Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma

Tomoyuki Iwasaki, Hidekazu Shirota, Eiji Hishinuma, Shinpei Kawaoka, Naomi Matsukawa, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Keigo Komine, Masanobu Takahashi, Chikashi Ishioka, Seizo Koshiba, Hisato Kawakami

International Journal of Molecular Sciences　26　(15)　7528-7528　2025年8月4日
出版者・発行元： MDPI AG
DOI： 10.3390/ijms26157528 　

eISSN：1422-0067

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Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC.
Randomized Phase III Trial of Ramucirumab Beyond Progression Plus Irinotecan in Patients With Ramucirumab-Refractory Advanced Gastric Cancer: RINDBeRG Trial. 国際誌

Daisuke Sakai, Shigenori Kadowaki, Ryohei Kawabata, Hiroki Hara, Hironaga Satake, Masazumi Takahashi, Atsushi Takeno, Hiroo Imai, Keiko Minashi, Takeshi Kawakami, Shogen Boku, Jin Matsuyama, Yasuhiro Sakamoto, Kentaro Sawada, Masato Kataoka, Hisato Kawakami, Toshio Shimokawa, Narikazu Boku, Taroh Satoh

Journal of clinical oncology : official journal of the American Society of Clinical Oncology　43　(19)　2196-2207　2025年7月

DOI： 10.1200/JCO.24.01119 　

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PURPOSE: Continuous use of antiangiogenic agents has demonstrated survival benefits in various cancers. This trial aimed to compare the efficacy and safety of ramucirumab plus irinotecan with irinotecan monotherapy as a third- or later-line treatment for patients with advanced or recurrent gastric or gastroesophageal cancer (AGC) that has progressed on previous ramucirumab-based chemotherapy. METHODS: Patients age 20 years and older with AGC, who had experienced disease progression during ramucirumab-based chemotherapy, were randomly assigned to receive either ramucirumab plus irinotecan or irinotecan monotherapy. The primary end point was overall survival (OS) expecting a hazard ratio (HR) of 0.77 (a power of 80% and a significance level of one-sided 0.05). Secondary end points included progression-free survival (PFS), response rate, disease control rate (DCR), and safety. RESULTS: Between February 2017 and August 2022, 402 patients in Japan were randomly assigned to receive ramucirumab plus irinotecan (n = 202) or irinotecan monotherapy (n = 200). The median OS was 9.4 months in the combination arm and 8.5 months in the monotherapy arm, with an adjusted HR of 0.91 (95% CI, 0.74 to 1.12; P = .49). PFS was improved (median, 3.8 v 2.8 months; HR, 0.72 [95% CI, 0.59 to 0.89]; P = .002), while the DCR was significantly better (64.4% v 52.1%; P = .03) with the combination therapy. The adverse events of the combination therapy were manageable. CONCLUSION: Adding ramucirumab to irinotecan does not provide a significant advantage in OS over irinotecan alone in patients with AGC who have progressed during ramucirumab-containing chemotherapy.
A multicenter Phase II study of mFOLFOX6 plus nivolumab for gastric cancer with severe peritoneal metastases: WJOG16322G. 国際誌

Munehiro Wakabayashi, Toshiki Masuishi, Takatsugu Ogata, Fumiyasu Hanamura, Mitsuhiro Furuta, Yoshiyuki Yamamoto, Kentaro Kawakami, Hidekazu Hirano, Yosuke Kito, Naoki Izawa, Naoki Takahashi, Toshihiko Matsumoto, Hisato Kawakami, Takayuki Ando, Keiko Minashi, Chiho Kudo, Kenichi Yoshimura, Kei Muro

Future oncology (London, England)　21　(17)　2135-2141　2025年7月

DOI： 10.1080/14796694.2025.2514935 　

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Advanced gastric cancer (AGC) patients with severe peritoneal metastases (SPM), characterized by massive ascites and/or inadequate oral intake, have a poor prognosis with the median overall survival of around 7 months, even when treated with fluorouracil/l-leucovorin plus oxaliplatin (mFOLFOX6), despite being a treatment options for these patients demonstrated in the WJOG10517G study. However, these patients were excluded from pivotal Phase III trials, including the CheckMate 649 study, which demonstrated the benefit of adding nivolumab to mFOLFOX6, due to tumor-related complications. Given the lack of data on the efficacy and safety of combining nivolumab with mFOLFOX6 for AGC patients with SPM, we initiated a Phase II study to evaluate this combination. The primary endpoint was the 1-year survival rate.Clinical trial registration: Japan Registry of Clinical Trials (jRCTs) 041220164.
Phase II Study (NO LIMIT, WJOG13320G) of First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability–High Advanced Gastric or Esophagogastric Junction Cancer 国際誌

Hisato Kawakami, Shigenori Kadowaki, Akitaka Makiyama, Masahiro Tsuda, Kenro Hirata, Naotoshi Sugimoto, Nozomu Machida, Hiroki Hara, Hidekazu Hirano, Taito Esaki, Yoshito Komatsu, Shuichi Hironaka, Yukari Kobayashi, Kazuhiro Kakimi, Yasutaka Chiba, Narikazu Boku, Ichinosuke Hyodo, Kei Muro

Journal of Clinical Oncology　43　(19)　2184-2195　2025年7月

DOI： 10.1200/JCO-24-02463 　

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PURPOSE: Microsatellite instability-high (MSI-H) advanced gastric or esophagogastric junction cancer (AGC), accounting for 5%-6% of all AGC cases, has shown an enhanced responsiveness to immunotherapy. We performed a single-arm phase II study to evaluate the combination of nivolumab (NIVO) and low-dose (LD) ipilimumab (IPI) for first-line treatment of MSI-H AGC. PATIENTS AND METHODS: Patients with MSI-H AGC received NIVO (240 mg once every 2 weeks) and IPI (1 mg/kg once every 6 weeks). The primary end point was overall response rate (ORR) assessed by blinded independent central review. Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and biomarker analysis. MSI-H status was confirmed with an MSI-IVD Kit (Falco). RESULTS: Twenty-nine patients were enrolled. The ORR was 62.1% (95% CI, 42.3 to 79.3), with a complete response rate of 10.3%. The DCR was 79.3% (95% CI, 60.3 to 92.0). Treatment-related adverse events (TRAEs) of any grade occurred in 93.1% of patients, with those of grade ≥3 manifesting in 37.9% of patients. At the data cutoff (median follow-up of 9.0 months), treatment had been discontinued in 21 patients, with such discontinuation being due to TRAEs in 12 (41.4%) patients. However, after exclusion of one patient with progressive disease, the remaining 11 patients showed long-term antitumor efficacy after treatment discontinuation (range of response duration, 0.9+ to 15.6+ months). The median PFS was 13.8 months (95% CI, 13.7 months to not reached [NR]) and the median OS was NR (95% CI, 13.7 months to NR), with a 12-month OS rate of 79.5%. CONCLUSION: NIVO plus LD-IPI showed robust and durable antitumor efficacy as a first-line treatment for MSI-H AGC. Although TRAEs often led to treatment discontinuation, treatment efficacy was subsequently sustained in most patients.
Phase I/II Study of Neoadjuvant Chemoradiotherapy Consisting of S-1 and Cisplatin for Patients with Clinically Resectable Type 4 or Large Type 3 Gastric Cancer (OGSG1205). 国際誌

Masayuki Shinkai, Motohiro Imano, Masaki Yokokawa, Ryo Tanaka, Jin Matsuyama, Toshio Shimokawa, Hisato Kawakami, Taroh Satoh, Takushi Yasuda, Hiroshi Furukawa

Annals of surgical oncology　32　(4)　2651-2661　2025年4月

DOI： 10.1245/s10434-024-16845-x 　

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BACKGROUND: To improve the prognosis of clinically resectable type 4 or large type 3 gastric cancer (GC), we performed a phase I/II study of neoadjuvant-radiotherapy combined with S-1 plus cisplatin. PATIENTS AND METHODS: Phase I, with a standard 3 + 3 dose-escalation design, was performed to define the recommended phase II dose. Efficacy and safety were evaluated in phase II. The three dose levels were as follows: level 0, S-1 60 mg/m2 on days 1-14 plus cisplatin 60 mg/m2 on day 1; level 1, S-1 80 mg/m2 on days 1-14 plus cisplatin 60 mg/m2 on day 1; and level 2, S-1 80 mg/m2 on days 1-14 and 22-35, plus cisplatin 60 mg/m2 on days 1 and 22. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks. RESULTS: A total of six patients were enrolled in the phase I study. Dose-limiting toxicity was observed at level 2; level 1 was established as the recommended phase II dose. In phase II, 20 patients were enrolled from November 2012 to April 2018. Grade 3/4 leukopenia and nonhematologic adverse events occurred in 35% and 5% of the patients, respectively. In total, 19 patients underwent the protocol surgery; 2 (10.5%) achieved a pathological complete response. There were no treatment-related deaths; 3- and 5-year overall survival rates were 70.0 and 50.0%, respectively. CONCLUSIONS: Neoadjuvant chemoradiotherapy with S-1 plus cisplatin is a safe and promising treatment for clinically resectable type 4 or large type 3 GC.
A phase 2 study of adjuvant chemotherapy with 5-fluorouracil/leucovorin and oxaliplatin after lung metastasectomy for colorectal cancer (WJOG5810G). 国際誌

Nozomu Machida, Takehiro Okumura, Narikazu Boku, Junji Kishimoto, Tomohiro Nishina, Koichi Suyama, Yasuhisa Ohde, Katsunori Shinozaki, Hideo Baba, Shinya Tokunaga, Hisato Kawakami, Takashi Tsuda, Masahito Kotaka, Hiroyuki Okuda, Hisateru Yasui, Kentaro Yamazaki, Shuichi Hironaka, Kei Muro, Ichinosuke Hyodo

Cancer　131　(7)　e35807　2025年4月1日

DOI： 10.1002/cncr.35807 　

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BACKGROUND: The clinical significance of adjuvant chemotherapy after lung metastasectomy for colorectal cancer remains unknown. This phase 2 study evaluated adjuvant chemotherapy with modified 5-fluorouracil/leucovorin and oxaliplatin (mFOLFOX6) after lung metastasectomy. METHODS: Eligibility criteria included colorectal adenocarcinoma, first curative resection of ≤4 lung metastases, and no prior chemotherapy. Treatment consisted of 12 cycles of mFOLFOX6. The primary endpoint was the 5-year overall survival (OS) rate, with the expectation of 50% (threshold, 35%) and a planned sample size of 100 (90% power; alpha error, 5%). RESULTS: Fifty-two patients were enrolled between July 2011 and July 2014; patient enrollment was closed prematurely because of slow accrual. Excluding four ineligible patients, the characteristics of the 48 patients in the efficacy analysis set were a median age of 62 years (range, 43-75 years), Eastern Cooperative Oncology Group performance status of 0 in 45 patients, prior resection of extrathoracic metastasis in four patients, and postoperative carcinoembryonic antigen within normal range in 43 patients; the status of lung metastasis was single in 34 patients, unilateral in 40 patients, and metachronous in 41 patients; and a disease-free interval between primary tumor resection and diagnosis of lung metastasis of <2 years in 33 patients. The 5-year OS rate was 85.2% (95% confidence interval [CI], 71.4%-92.6%), and the 5-year disease-free survival rate was 60.2% (95% CI, 44.9%-72.4%). Forty-one of the 52 patients (78.8%) in the safety analysis set completed 12 cycles of mFOLFOX6. Grade ≥3 adverse events were neutropenia (50.0%), fatigue (7.7%), peripheral sensory neuropathy (7.7%), and other (<5%). CONCLUSIONS: Adjuvant chemotherapy with mFOLFOX6 is feasible, and may be effective after lung metastasectomy for colorectal cancer.
Chromosomal Instability Is Associated with cGAS–STING Activation in EGFR-TKI Refractory Non-Small-Cell Lung Cancer 国際誌

Kimio Yonesaka, Takashi Kurosaki, Junko Tanizaki, Hisato Kawakami, Kaoru Tanaka, Osamu Maenishi, Shiki Takamura, Kazuko Sakai, Yasutaka Chiba, Takeshi Teramura, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Yasuki Kamai, Takashi Kagari, Kazuto Nishio, Kazuhiro Kakimi, Hidetoshi Hayashi

Cells　14　(6)　2025年3月17日

DOI： 10.3390/cells14060447 　

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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard therapies for EGFR-mutated non-small-cell lung cancer (NSCLC); however, their efficacy is inconsistent. Secondary mutations in the EGFR or other genes that lead to resistance have been identified, but resistance mechanisms have not been fully identified. Chromosomal instability (CIN) is a hallmark of cancer and results in genetic diversity. In this study, we demonstrated by transcriptomic analysis that CIN activates the cGAS-STING signaling pathway, which leads to EGFR-TKI refractoriness in a subset of EGFR-mutated NSCLC patients. Furthermore, EGFR-mutated H1975dnMCAK cells, which frequently underwent chromosomal mis-segregation, demonstrated refractoriness to the EGFR-TKI osimertinib compared to control cells. Second, H1975dnMCAK cells exhibited activation of cGAS-STING signaling and its downstream signaling, including tumor-promoting cytokine IL-6. Finally, chromosomally unstable EGFR-mutated NSCLC exhibited enhanced epithelial-mesenchymal transition (EMT). Blockade of cGAS-STING-TBK1 signaling reversed EMT, resulting in restored susceptibility to EGFR-TKIs in vitro and in vivo. These results suggest that CIN may lead to the activation of cGAS-STING signaling in some EGFR-mutated NSCLC, resulting in EMT-associated EGFR-TKI resistance.
Prevalence and clinicopathological features of microsatellite instability-high metastatic or recurrent gastric and esophagogastric junction cancer: WJOG13320GPS.

Azusa Komori, Shuichi Hironaka, Shigenori Kadowaki, Seiichiro Mitani, Mitsuhiro Furuta, Takeshi Kawakami, Akitaka Makiyama, Naoki Takegawa, Keiji Sugiyama, Hidekazu Hirano, Takayuki Ando, Tomohiro Matsushima, Akihiko Chida, Tomomi Kashiwada, Masato Komoda, Toshihiko Matsumoto, Hisanobu Oda, Hiroshi Yabusaki, Hisato Kawakami, Kentaro Yamazaki, Narikazu Boku, Ichinosuke Hyodo, Kenichi Yoshimura, Kei Muro

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　28　(2)　301-308　2025年3月

DOI： 10.1007/s10120-024-01579-2 　

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BACKGROUND: Microsatellite instability (MSI)-high tumors represent a distinct, small-fraction subtype in esophagogastric junction cancer or gastric cancer (GC), yet their clinical significance remains poorly understood. This study aimed to investigate the prevalence and clinicopathological features of chemotherapy-naïve metastatic or recurrent MSI-high GC as a prescreening study for a phase II trial of nivolumab plus ipilimumab. METHODS: Key inclusion criteria included metastatic or recurrent adenocarcinoma of GC, ECOG performance status of 0 or 1, and no prior systemic therapy for metastatic or recurrent disease. MSI status was tested using multiplex PCR fragment analysis (MSI Testing Kit, FALCO). The primary endpoint was the prevalence of MSI-high GC. RESULTS: Between October 2020 and October 2022, 930 eligible patients from 75 centers in Japan were analyzed. The prevalence of MSI-high GC was 5.6% (95% CI 4.2-7.3). MSI-high GC was more frequently observed in females than males (9.6% vs 3.8%, p < 0.001), patients aged ≥ 70 years compared to those < 70 years (8.0% vs 2.8%, p < 0.001), in the lower stomach than other locations (10.5% vs 3.2%, p < 0.001), HER2-negative tumors than HER2-positive tumors (6.5% vs 1.8%, p = 0.02), and in patients without liver metastasis than those with liver metastasis (6.9% vs 2.2%, p = 0.004). CONCLUSIONS: The prevalence of MSI-high tumors among chemotherapy-naïve patients with unresectable GC was 5.6%. These tumors were associated with female sex, older age, lower stomach, HER2-negative, and absence of liver metastasis. These findings would help assuming MSI-high tumors and may have significant implications for clinical practice and studies targeting this GC subtype.
A Phase II Trial of Trastuzumab Combined With Irinotecan in Patients With Advanced HER2-positive Chemotherapy-refractory Gastric Cancer (OGSG1203 HERBIS-5): Final Results. 国際誌

Junji Kawada, Daisuke Sakai, Yutaka Kimura, Motohiro Hirao, Kazuhiro Nishikawa, Naotoshi Sugimoto, Yoshio Oka, Shunji Endo, Yutaka Isozaki, Jin Matsuyama, Ryohei Kawabata, Tomono Kawase, Kazumasa Fujitani, Yukinori Kurokawa, Hisato Kawakami, Toshio Shimokawa, Taroh Satoh

Anticancer research　45　(3)　1077-1085　2025年3月

DOI： 10.21873/anticanres.17495 　

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BACKGROUND/AIM: Irinotecan is a key drug for patients with advanced gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in patients with advanced human epidermal growth factor receptor type 2 (HER2)-positive chemotherapy-refractory gastric cancer. PATIENTS AND METHODS: Eligibility criteria included unresectable or recurrent HER2-positive gastric cancer patients who were refractory to at least one regimen of chemotherapy. Irinotecan was administered at a dose of 150 mg/m2 every 2 weeks, and trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. The primary endpoint was the disease control rate (DCR). The secondary endpoints were adverse events (AEs), overall response rate (ORR), time-to-treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty patients were enrolled, of whom 18 previously received a single chemotherapy regimen whereas 12 received two or more regimens. As one patient withdrew before the study treatment, 29 patients were assessable for efficacy and safety. The DCR was 65.5%, and the ORR was 20.7%. The median PFS and OS were 3.7 and 7.5 months, respectively. The major grade 3/4 AEs were neutropenia (24%), anemia (24%), leukopenia (21%), anorexia (11%), fatigue (14%), hypoalbuminemia (24%), and hypokalemia (14%). One treatment-related death occurred. CONCLUSION: These findings indicate that irinotecan plus trastuzumab is feasible with modest potential efficacy against chemotherapy-refractory advanced HER2-positive gastric cancer.
Publisher Correction: HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01 国際誌

Salvatore Siena, Kanwal Raghav, Toshiki Masuishi, Kensei Yamaguchi, Tomohiro Nishina, Elena Elez, Javier Rodriguez, Ian Chau, Maria Di Bartolomeo, Hisato Kawakami, Fumitaka Suto, Makito Koga, Koichiro Inaki, Yusuke Kuwahara, Issey Takehara, Daniel Barrios, Kojiro Kobayashi, Axel Grothey, Takayuki Yoshino

Nature Communications　16　(1)　704-704　2025年1月15日

DOI： 10.1038/s41467-025-56170-9 　

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DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA.
Prognostic impact of gene alterations via homologous recombination DNA repair gene alteration status in pancreatic ductal adenocarcinoma. 国際誌

Yusuke Kawanaka, Chiaki Inagaki, Masaki Okura, Seiichiro Mitani, Takayuki Takahama, Kimio Yonesaka, Yasutaka Chiba, Kazuhiko Nakagawa, Hisato Kawakami, Hidetoshi Hayashi

Frontiers in medicine　12　1570731-1570731　2025年

DOI： 10.3389/fmed.2025.1570731 　

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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with limited treatment options and poor prognosis. Recent advances in cancer genomic analysis enable the identification of actionable gene alterations, opening new opportunities for personalized therapy. Among these, homologous recombination DNA repair (HRR) gene alterations are associated with distinct biological behavior, favorable prognosis, and increased sensitivity to platinum-based chemotherapy. However, the prognostic impact of coexisting mutations in key driver genes-KRAS, TP53, CDKN2A, and SMAD4-within HRR-altered PDAC remains poorly understood. METHODS: We retrospectively analyzed PDAC patients who underwent genomic profiling testing with FoundationOne® CDx between June 2019 and December 2021 through the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. We compared the prevalence and prognostic significance of key gene alterations between HRR-altered and HRR-wild-type (WT) tumors. RESULTS: Of 2,381 PDAC patients, 274 (11.5%) harbored HRR alterations. These patients showed significantly longer overall survival (OS) than those with HRR-WT tumors (HR = 0.66, p = 0.002). The frequencies of KRAS, TP53, and CDKN2A mutations were less frequent in HRR-altered tumors. TP53 mutation was independently associated with poorer OS across both HRR subgroups, while CDKN2A alteration was a poor prognostic factor in HRR-WT tumors. Interestingly, SMAD4 alteration was linked to improved survival in the HRR-altered group. CONCLUSION: HRR-altered PDAC has a distinct genomic profile and is associated with a favorable prognosis. Our findings demonstrate that coexisting alterations are significant prognostic factors in both HRR-altered and HRR-wild-type tumors. These results highlight the clinical relevance of incorporating comprehensive genomic profiling into routine care to stratify patient prognosis better and inform individualized treatment strategies in PDAC.
Short-term outcomes of a phase II trial of perioperative capecitabine plus oxaliplatin therapy for advanced gastric cancer with extensive lymph node metastases (OGSG1701).

Yutaka Kimura, Naotoshi Sugimoto, Shunji Endo, Ryohei Kawabata, Jin Matsuyama, Atsushi Takeno, Masato Nakamura, Hiroki Takeshita, Hironaga Satake, Shigeyuki Tamura, Daisuke Sakai, Hisato Kawakami, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　28　(1)　112-121　2025年1月

DOI： 10.1007/s10120-024-01564-9 　

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BACKGROUND: The prognosis of advanced gastric cancer (GC) with extensive lymph node (LN) metastasis treated with surgery alone remains poor. We conducted a multicenter phase II study to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin (CapeOx) therapy in patients with advanced GC with extensive LN metastases. PATIENTS AND METHODS: Patients with histologically proven HER2-negative or unknown gastric adenocarcinoma with paraaortic LN (PALN) metastases and/or bulky LN metastases located at the celiac axis, common hepatic artery, and/or splenic artery were included in the study. Patients received three cycles of preoperative CapeOx every 3 weeks, followed by five cycles of postoperative CapeOx after gastrectomy with D2 or D2 + including PALN dissection. The primary endpoint was the response rate (RR) according to the RECIST v1.0 criteria. RESULTS: Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. Complete response, partial response, stable disease, and progressive disease occurred in zero, 20, eight, and one patient, respectively. One patient was not evaluated. The RR was 66.7% (90% confidence interval, 50.1-80.7%; one-sided P = 0.049). The preoperative chemotherapy completion rate and the curative resection rate were 96.7% and 93.3%, respectively. The minor (grade ≥ 1b) pathological RR was 66.7%. Grade 3 adverse events of preoperative chemotherapy included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10.0%. One treatment-related death occurred due to postoperative complications. CONCLUSION: Preoperative CapeOx chemotherapy showed a favorable RR, curative resection rate, and acceptable adverse events in patients with advanced GC with extensive LN metastasis. REGISTRATION NUMBER: UMIN000028749 and jRCTs051180186.
Salvage-line of Capecitabine Plus Oxaliplatin Therapy (XELOX) for Patients With Inoperable/Advanced Gastric Cancer Resistant/Intolerant to Cisplatin (OGSG1403). 国際誌

Naotoshi Sugimoto, Junji Kawada, Yoshio Oka, Shugo Ueda, Kohei Murakami, Kazuhiro Nishikawa, Yukinori Kurokawa, Kazumasa Fujitani, Hisato Kawakami, Shunji Endo, Daisuke Sakai, Toshio Shimokawa, Taroh Satoh

Anticancer research　45　(1)　307-313　2025年1月

DOI： 10.21873/anticanres.17418 　

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BACKGROUND/AIM: No prospective study has evaluated salvage chemotherapy with capecitabine plus oxaliplatin (XELOX) in patients with gastric cancer who are resistant to or intolerant of cisplatin. PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II study was conducted at six centers in Japan, enrolling patients with metastatic or advanced gastric cancer resistant to or intolerant of fluoropyrimidine, cisplatin, taxane, and irinotecan. Capecitabine 1,000 mg/m2 was administered orally twice daily for 14 days, followed by a 7-day rest period. Oxaliplatin 130 mg/m2 was administered intravenously on day one. The primary endpoint was disease control rate (DCR). Secondary endpoints included response rate (RR), progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: The study was terminated prematurely due to poor accrual, with 12 patients enrolled. Eight patients demonstrated resistance to prior cisplatin, while four experienced unacceptable toxicity. The median age was 64 years, and eight were male. Four, six, and two patients had Eastern Cooperative Oncology Group performance status 0, 1, and 2, respectively. Among 10 evaluable patients, DCR was 90%, with an RR of 30%. Median PFS, TTF, and OS were 4.2 months [95% confidence interval (CI)=1.4-5.3], 4.1 months (95%CI=1.4-4.4), and 7.1 months (95%CI=2.3-10.1), respectively. The most frequently reported grade 3-4 adverse events were fatigue (20%) and hypokalemia (20%). No treatment-related deaths occurred. CONCLUSION: Salvage chemotherapy with XELOX may offer clinical benefits for patients with metastatic or advanced gastric cancer resistant to or intolerant of cisplatin.
Phase II Trial of Capecitabine Plus Bevacizumab for Elderly Patients With Metastatic Colorectal Cancer: OGSG 1102. 国際誌

Toshifumi Yamaguchi, Motoki Yoshida, Koichi Taira, Shinya Tokunaga, Takeshi Kato, Masato Nakamura, Naotoshi Sugimoto, Soichi Fumita, Masayoshi Yasui, Yasuhiro Miyake, Hisato Kawakami, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

In vivo (Athens, Greece)　39　(3)　1505-1513　2025年

DOI： 10.21873/invivo.13950 　

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BACKGROUND/AIM: The combination of capecitabine and bevacizumab is a standard first-line chemotherapy regimen for vulnerable patients with unresectable colorectal cancer. However, the safety and efficacy of this regimen in Japanese patients have not been sufficiently investigated. PATIENTS AND METHODS: This phase II study included patients aged ≥76 years or those aged 65-75 years who were unsuitable for intensive chemotherapy. Capecitabine at 2000 mg/m2/day (days 1-14) plus bevacizumab at 7.5 mg/kg (day 1) were administered every 3 weeks. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, response rate, disease control rate, and toxicities. RESULTS: Thirty-six patients were enrolled between July 2011 and July 2014, of whom 33 were included in the analysis. The median patient age was 78 years (range=67-86 years). A total of 28 patients had a performance status of 0 or 1, and five of 2. The median progression-free and overall survival were 10.3 (95% confidence interval=9.2-15.4) and 27.9 (95% confidence interval=24.2-50.1) months, respectively. The response and disease control rates were 30.3% and 91.0%, respectively. The major grade 3 or 4 toxicities were hypertension (n=12, 36%) and hand-foot syndrome (n=4, 12%). One patient experienced a grade 4 gastrointestinal perforation. CONCLUSION: The combination of capecitabine and bevacizumab demonstrated favorable efficacy and tolerability in Japanese patients with metastatic colorectal cancer who were unsuitable for intensive chemotherapy.
Phase I study of neoadjuvant chemoradiotherapy with S-1 for clinically resectable type 4 or large type 3 gastric cancer in elderly patients aged 75 years and older (OGSG1303). 国際誌

Masayuki Shinkai, Motohiro Imano, Masaki Yokokawa, Jin Matsuyama, Yutaka Kimura, Toshio Shimokawa, Hisato Kawakami, Taroh Satoh, Takushi Yasuda, Hiroshi Furukawa

Medical oncology (Northwood, London, England)　42　(1)　31-31　2024年12月19日

DOI： 10.1007/s12032-024-02583-3 　

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Purpose The prognosis for type 4 and large type 3 gastric cancer (GC) is extremely poor, especially in elderly patients (≥ 75 years). To improve the prognosis of these types of GC, we performed a phase I study to determine the recommended dose (RD) of S-1 combined with neoadjuvant radiotherapy. Methods Patients with clinically resectable type 4 and large type 3 GC were enrolled to successive cohorts in a conventional 3 + 3 design. Three dose levels were designed, as follows: level 0: S-1 60 mg/m2/day on Days 1-14; level 1: S-1 80 mg/m2/day on Days 1 -14; level 2: S-1 80 mg/m2/day on Days 1-14 and Days 22-35. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks. Results Ten patients were enrolled from July 2014 to August 2018. Six patients were registered at level 1, and one patient developed a dose limiting toxicity as gastric stenosis (grade 3). Two of four patients enrolled at level 2 developed dose limiting toxicity (inability to receive S-1 for hematological reasons). Therefore, the RD was determined as level 1. All patients underwent the protocol surgery; one patient underwent R1 resection because of positive peritoneal washing cytology. There were no treatment-related deaths, and the pathological response rate was 80%. The 5-year overall- and progression-free survival rates were both 60.0%. Conclusion The RD was determined as level 1. A phase II trial using the RD should be initiated.
当院における免疫関連有害事象対策チーム「imNET」の活動について

藤原季美子, 高濱隆幸, 磯本晃佑, 渡邉諭美, 稲垣千晶, 三谷誠一郎, 谷崎潤子, 吉田健史, 田中薫, 川上尚人, 岩朝勤, 米阪仁雄, 林秀敏, 萩原智, 西山理, 桑原基, 柳江正嗣, 遠藤みゆき, 竹久志穂, 高橋直美

肺癌　64　(7)　950-950　2024年12月
出版者・発行元： (NPO)日本肺癌学会
ISSN：0386-9628

eISSN：1348-9992
Evaluation of immune checkpoint inhibitor efficacy for solid tumors withCD274(PD-L1 gene) amplification identified by comprehensive genomic profiling: retrospective study based on a nationwide database 国際誌

Tomohiro Nakayama, Takayuki Takahama, Yasutaka Chiba, Naoki Shiraishi, Hisato Kawakami, Kimio Yonesaka, Kazuhiko Nakagawa, Hidetoshi Hayashi

Journal for ImmunoTherapy of Cancer　12　(12)　2024年12月

DOI： 10.1136/jitc-2024-010130 　

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BACKGROUND: Amplification of the programmed cell death-ligand 1 gene (CD274) is highly prevalent and associated with a high response rate to immune checkpoint inhibitors (ICIs) in lymphomas, and is also a potential biomarker for ICI treatment of solid tumors. However, the efficacy of ICIs for solid tumors with CD274 amplification identified by comprehensive genomic profiling (CGP) has been unclear. We here examined ICI efficacy for solid tumors with CD274 amplification identified by CGP in a national database. METHODS: We retrospectively analyzed data from the Center for Cancer Genomics and Advanced Therapeutics database containing 60,155 CGP test results for individuals with solid tumors. Only clinical data from patients treated with ICIs alone (not those undergoing concomitant therapy with molecularly targeted or cytotoxic chemotherapeutic agents) were evaluated. We matched 48 patients in the CD274 amplification-positive group with 170 patients in the CD274 amplification-negative group in a 1:4 ratio based on tumor type, histology, treatment, and age. Overall survival (OS), time to next treatment (TTNT), and response rate were evaluated as treatment outcomes in the two groups. RESULTS: OS was similar in the CD274-amplified and matched CD274-non-amplified groups (median of 22.1 vs 26.3 months, respectively; HR of 0.92 with a 95% CI of 0.55 to 1.54; p=0.075). TTNT tended to be longer in the CD274-amplified group than in the matched CD274-non-amplified group (median of 16.5 vs 14.0 months; HR of 0.63 with a 95% CI of 0.37 to 1.08; p=0.091). The objective response rate was 33.3% and 18.4% (difference of 14.9%, with a 95% CI of -0.2% to 31.6%), and the disease control rate was 63.9% and 41.1% (difference of 22.8%, with a 95% CI of 5.1% to 40.4%), in the CD274-amplified and matched CD274-non-amplified groups, respectively. CONCLUSIONS: The number of patients with solid tumors positive for CD274 amplification in this analysis is the largest to date, and our results suggest that such gene amplification may be associated with the outcome of ICI treatment in such individuals. CD274 amplification identified by CGP may therefore be a predictor of ICI efficacy for solid tumors. TRIAL REGISTRATION NUMBER: UMIN000029779.
Correction: Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study).

Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　28　(1)　62-62　2024年11月28日

DOI： 10.1007/s10120-024-01570-x 　
<scp>JAK</scp> Inhibitor Upadacitinib Induces Remission in Refractory Immune‐Related Colitis Triggered by <scp>CTLA</scp>‐4 and <scp>PD</scp>‐1 Inhibitor Combination Therapy in Malignant Pleural Mesothelioma: A Case Report 国際誌

Masashi Kono, Yoriaki Komeda, Hisato Kawakami, Satoru Hagiwara, George Tribonias, Kohei Handa, Shunsuke Omoto, Mamoru Takenaka, Hiroshi Kashida, Naoko Tsuji, Masatoshi Kudo

Cancer Reports　7　(10)　e70032　2024年10月28日
出版者・発行元： Wiley
DOI： 10.1002/cnr2.70032 　

ISSN：2573-8348

eISSN：2573-8348

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ABSTRACT Background Immune checkpoint inhibitors have demonstrated efficacy against various cancers; however, there is a rising incidence of immune‐related colitis. Some cases of immune‐related colitis prove resistant to treatment, even with the administration of glucocorticoids or infliximab, and there is currently no established standard treatment for such cases. Case The patient, a 73‐year‐old male, had undergone combination therapy for malignant pleural mesothelioma for 2 years, utilizing both ipilimumab (a CTLA‐4 inhibitor) and nivolumab (a PD‐1 inhibitor). Unfortunately, the treatment led to side effects, specifically immune‐related adverse event (irAE) enterocolitis. Steroid and infliximab treatment failed to improve the patient's condition. Treatment with tacrolimus was attempted, but the patient remained unresponsive. Subsequently, 45 mg of upadacitinib, a Janus kinase (JAK) inhibitor, was administered. Symptoms improved rapidly following upadacitinib administration, and endoscopy also revealed positive results. With the increasing incidence of immune‐related colitis, some patients have become resistant to treatment with glucocorticoids and infliximab. In this case, the irAE enterocolitis was improved by upadacitinib administration. Conclusion In cases where immune‐related colitis proves resistant to treatment with glucocorticoids, infliximab, or tacrolimus, upadacitinib represents a potential option as a JAK inhibitor.
Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study).

Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　2024年10月10日

DOI： 10.1007/s10120-024-01555-w 　

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BACKGROUND: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd. METHODS: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs). RESULTS: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected. CONCLUSIONS: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice. CLINICAL TRIAL REGISTRATION: UMIN000049032.
ペムブロリズマブが奏効したTMB-Hを有する限局型小細胞肺がん早期再発の1例

大倉將生, 稲垣千晶, 高濱隆幸, 谷崎潤子, 川上尚人, 米阪仁雄, 中川和彦, 林秀敏

日本癌治療学会学術集会抄録集　62回　P18-1　2024年10月
出版者・発行元： (一社)日本癌治療学会
切除不能大腸癌に対するFOLFIRI/FOLFOXIRI+ラムシルマブ WJOG9216G試験の最終解析

川上尚人, 木藤陽介, 庄司広和, 山田武史, 對馬隆浩, 三谷誠一郎, 白石和寛, 安井久晃, 原浩樹, 下嵜啓太郎, 西尾和人, 吉村健一, 廣中秀一, 室圭

日本癌治療学会学術集会抄録集　62回　EN1-5　2024年10月
出版者・発行元： (一社)日本癌治療学会
Phase 1b/2 study of the liposomal formulation of eribulin (E7389-LF) in combination with nivolumab: Results from the phase 2 esophageal cancer cohort. 国際誌

Takashi Oshima, Sachiko Yamamoto, Hisato Kawakami, Tomoki Makino, Akihito Kawazoe, Toshiki Masuishi, Takahiro Tsushima, Motohiro Hirao, Masahiro Tsuda, Kaori Hino, Noboru Yamamoto, Hiroki Hara, Shota Kaname, Daiko Matsuoka, Yohei Otake, Keisuke Yasuda, Takao Takase, Shuya Takashima, Taro Semba, Akira Ooki

BJC reports　2　(1)　66-66　2024年9月4日

DOI： 10.1038/s44276-024-00066-6 　

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BACKGROUND: Esophageal cancer is one of the most common types of cancer in Japan. Herein, we report the efficacy and safety of E7389-LF plus the immune checkpoint inhibitor, nivolumab, from the esophageal cancer cohort of the phase 2 part of Study 120. METHODS: Eligible patients received E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously Q3W. The primary objective was to evaluate the objective response rate (ORR); other objectives included safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 35 Japanese patients enrolled, 7 (20.0%) had a partial response as their best overall response, and 14 (40.0%) had stable disease. The ORR was 20.0% (95% CI 8.4-36.9). The duration of response was 5.6 months (95% CI 1.7-not estimable [NE]). The median PFS was 2.81 months (95% CI 1.31-4.17). The median OS was not reached (95% CI 6.54 months-NE). The most common treatment-emergent adverse events were neutropenia (65.7%), pyrexia (60.0%), and leukopenia (57.1%). Select plasma endothelial cell markers levels increased from day 1 of cycle 1 and changes were pronounced between days 8-15 of each cycle. CONCLUSIONS: E7389-LF plus nivolumab showed antitumor activity in patients with unresectable and pretreated esophageal cancer and should be evaluated further in a broader population. CLINICAL TRIAL REGISTRATION: NCT04078295.
Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in circulating tumor DNA for the treatment of refractory gastrointestinal stromal tumors. 国際誌

Tadayoshi Hashimoto, Yoshiaki Nakamura, Yoshito Komatsu, Satoshi Yuki, Naoki Takahashi, Naohiro Okano, Hidekazu Hirano, Koushiro Ohtsubo, Takashi Ohta, Eiji Oki, Tomohiro Nishina, Hisateru Yasui, Hisato Kawakami, Taito Esaki, Nozomu Machida, Ayako Doi, Shogen Boku, Toshihiro Kudo, Yoshiyuki Yamamoto, Akiyoshi Kanazawa, Tadamichi Denda, Masahiro Goto, Naoko Iida, Hiroshi Ozaki, Taro Shibuki, Mitsuho Imai, Takao Fujisawa, Hideaki Bando, Yoichi Naito, Takayuki Yoshino

BJC reports　2　(1)　54-54　2024年7月25日

DOI： 10.1038/s44276-024-00073-7 　

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BACKGROUND: While advanced gastrointestinal stromal tumors (GISTs) are primarily treated with tyrosine kinase inhibitors (TKIs), acquired resistance from specific mutations in KIT or PDGFRA frequently occurs. We aimed to assess the utility of circulating tumor DNA (ctDNA) as a modality of therapeutic decision-making in advanced GIST. METHODS: We conducted a pooled analysis of SCRUM-Japan studies for advanced GIST patients. We compared patient characteristics analyzed with tissue and blood samples, assessed gene alteration profiles, and evaluated prognostic implications from ctDNA status. RESULTS: In 133 patients, tissue and blood samples were analyzed for 89 and 44 patients, respectively. ctDNA was detected in 72.7% of cases; no prior treatment or progressive disease was significantly associated with ctDNA-positivity. ctDNA-positive patients had significantly shorter progression-free survival compared with ctDNA-negative patients (hazard ratio = 3.92; P = 0.007). ctDNA genotyping revealed a complex landscape of gene alterations, characterized by multi-exonic mutations in KIT, compared with tissue-based analysis. Patients who received TKIs matched to the identified KIT mutation in ctDNA demonstrated significantly longer PFS than those with unmatched treatment (median, 8.23 vs. 2.43 months; P < 0.001). CONCLUSIONS: ctDNA-based analysis facilitates assessment of disease status and genomic profiles, thus potentially assisting in identifying optimal therapeutic strategies for advanced GIST patients.
QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. FOLFOXIRI+bevacizumab as first-line treatment in patients with mCRC. 国際誌

Hideaki Bando, Daisuke Kotani, Hironaga Satake, Tetsuya Hamaguchi, Manabu Shiozawa, Masahito Kotaka, Toshiki Masuishi, Hisateru Yasui, Yoshinori Kagawa, Yoshito Komatsu, Eiji Oki, Yoshiyuki Yamamoto, Hisato Kawakami, Toshihiro Misumi, Hiroya Taniguchi, Kentaro Yamazaki, Kei Muro, Takayuki Yoshino, Takeshi Kato, Akihito Tsuji

Med (New York, N.Y.)　2024年6月14日

DOI： 10.1016/j.medj.2024.05.012 　

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BACKGROUND: The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC). METHODS: In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80 < HR < 1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes. FINDINGS: Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met its primary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9 months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR 1.114 [0.80 < HR < 1.25], p = 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%). CONCLUSION: CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC. FUNDING: Chugai Pharmaceutical Co., Ltd.
Nivolumab plus chemotherapy or ipilimumab versus chemotherapy in patients with advanced esophageal squamous cell carcinoma (CheckMate 648): 29-month follow-up from a randomized, open-label, phase III trial. 国際誌

Ken Kato, Yuichiro Doki, Ian Chau, Jianming Xu, Lucjan Wyrwicz, Satoru Motoyama, Takashi Ogata, Hisato Kawakami, Chih-Hung Hsu, Antoine Adenis, Farid El Hajbi, Maria Di Bartolomeo, Maria Ignez Braghiroli, Eva Holtved, Tomoki Makino, Mariela Blum Murphy, Carlos Amaya-Chanaga, Apurva Patel, Nan Hu, Yasuhiro Matsumura, Yuko Kitagawa, Jaffer Ajani

Cancer medicine　13　(9)　e7235　2024年5月

DOI： 10.1002/cam4.7235 　

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BACKGROUND: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS: A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.
Clinical practice guidelines for esophagogastric junction cancer: Upper GI Oncology Summit 2023.

Yuko Kitagawa, Satoru Matsuda, Takuji Gotoda, Ken Kato, Bas Wijnhoven, Florian Lordick, Pradeep Bhandari, Hirofumi Kawakubo, Yasuhiro Kodera, Masanori Terashima, Kei Muro, Hiroya Takeuchi, Paul F Mansfield, Yukinori Kurokawa, Jimmy So, Stefan Paul Mönig, Kohei Shitara, Sun Young Rha, Yelena Janjigian, Daisuke Takahari, Ian Chau, Prateek Sharma, Jiafu Ji, Giovanni de Manzoni, Magnus Nilsson, Paulo Kassab, Wayne L Hofstetter, Elizabeth Catherine Smyth, Sylvie Lorenzen, Yuichiro Doki, Simon Law, Do-Youn Oh, Khek Yu Ho, Tomoyuki Koike, Lin Shen, Richard van Hillegersberg, Hisato Kawakami, Rui-Hua Xu, Zev Wainberg, Naohisa Yahagi, Yeong Yeh Lee, Rajvinder Singh, Min-Hee Ryu, Ryu Ishihara, Zili Xiao, Chika Kusano, Heike Irmgard Grabsch, Hiroki Hara, Ken-Ichi Mukaisho, Tomoki Makino, Mitsuro Kanda, Eisuke Booka, Sho Suzuki, Waku Hatta, Motohiko Kato, Akira Maekawa, Akihito Kawazoe, Shun Yamamoto, Izuma Nakayama, Yukiya Narita, Han-Kwang Yang, Masahiro Yoshida, Takeshi Sano

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　27　(3)　401-425　2024年5月

DOI： 10.1007/s10120-023-01457-3 　
Anti-integrin αvβ6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis. 国際誌

Masataka Yokode, Masahiro Shiokawa, Hisato Kawakami, Takeshi Kuwada, Yoshihiro Nishikawa, Yuya Muramoto, Hiroki Kitamoto, Makoto Okabe, Hajime Yamazaki, Norihiro Okamoto, Toshihiro Morita, Kazuya Ohno, Risa Nakanishi, Ikuhisa Takimoto, Muneji Yasuda, Koki Chikugo, Shimpei Matsumoto, Hiroyuki Yoshida, Sakiko Ota, Takeharu Nakamura, Hirokazu Okada, Tomonori Hirano, Nobuyuki Kakiuchi, Tomoaki Matsumori, Shuji Yamamoto, Norimitsu Uza, Makoto Ooi, Yuzo Kodama, Tsutomu Chiba, Hidetoshi Hayashi, Hiroshi Seno

British journal of cancer　130　(9)　1552-1560　2024年5月

DOI： 10.1038/s41416-024-02647-1 　

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BACKGROUND: No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvβ6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis. METHODS: Serum anti-integrin αvβ6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvβ6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients. RESULTS: Anti-integrin αvβ6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls (P < 0.001). Patients with anti-integrin αvβ6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies (P < 0.001). Anti-integrin αvβ6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis (P = 0.001) and steroid resistance (P = 0.005). Anti-integrin αvβ6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvβ6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC. CONCLUSIONS: Anti-integrin αvβ6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.
New therapeutic target molecules for gastric and gastroesophageal junction cancer.

Hisato Kawakami

International journal of clinical oncology　2024年4月17日

DOI： 10.1007/s10147-024-02521-3 　

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Molecularly targeted therapy for receptor tyrosine kinases (RTKs) has faced limitations in gastric and gastroesophageal junction (G/GEJ) cancer except for HER2-targeted agents, possibly due to inappropriate assay selection that has hindered identification of sensitive patients, in addition to coexisting genetic abnormalities as well as intratumoral heterogeneity. Immunohistochemistry of RTKs has, thus, proved largely unsuccessful for patient selection, and detection of RTK gene amplification as a true oncogenic driver is problematic given the small numbers of affected individuals. FGFR2 amplification is associated with poor prognosis in G/GEJ cancer, and immunohistochemistry of the FGFR2b protein isoform has proved effective for the detection of such FGFR2-dependent tumors. Phase III and Ib/III trials of the FGFR2-targeted antibody bemarituzumab for G/GEJ cancer overexpressing FGFR2b are ongoing based on the promising result in a phase II trial, especially in cases with an FGFR2b positivity of ≥ 10%. Challenges to EGFR- and MET-targeted therapies are being tackled with antibody-drug conjugates (ADCs) and bispecific antibodies. CLDN18.2 is expressed in some G/GEJ tumors but lacks oncogenic driver potential, and the CLDN18.2-targeted antibody zolbetuximab prolonged the survival of CLDN18.2-positive G/GEJ cancer patients in phase III trials. Antibody-drug conjugates and ADCs that target CLDN18.2 are also being pursued for treatment of such patients. Similarly, targeting of nondriver molecules such as DKK1, TROP2, and CEACAM5 is under investigation in early-stage clinical trials. This shift in focus from target molecules with driver potential to markers for precise drug delivery should increase the number of possible targets in G/GEJ cancer.
Phase II Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Gastric Cancer Cohort. 国際誌

Akihito Kawazoe, Noboru Yamamoto, Naotoshi Sugimoto, Hisato Kawakami, Takashi Oshima, Kensei Yamaguchi, Kaori Hino, Motohiro Hirao, Yukinori Kurokawa, Takeshi Kawakami, Masahiro Tsuda, Hiroki Hara, Shota Kaname, Daiko Matsuoka, Yohei Otake, Keisuke Yasuda, Takao Takase, Shuya Takashima, Taro Semba, Kei Muro

Clinical cancer research : an official journal of the American Association for Cancer Research　30　(7)　1264-1272　2024年4月1日

DOI： 10.1158/1078-0432.CCR-23-1768 　

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PURPOSE: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin and has shown preliminary efficacy in the treatment of gastric cancer. Study 120, a phase Ib/II open-label study, assessed efficacy and safety of E7389-LF in combination with nivolumab, a programmed cell death (PD)-1 inhibitor. This report focuses on the gastric cancer cohort within the expansion phase. PATIENTS AND METHODS: Eligible patients had unresectable, measurable gastric cancer, progression following a platinum drug plus fluoropyrimidine (1L), and a taxane-containing regimen (2L). The primary objective of the expansion phase was objective response rate, secondary objectives included safety and PFS, and exploratory objectives included overall survival and biomarker evaluation. Patients received E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks, both as intravenous infusions. Tumor responses were assessed every 6 weeks by the investigators per RECIST v1.1. Plasma and tumor biomarkers were assessed. RESULTS: In the 31 patients who received E7389-LF in combination with nivolumab, the objective response rate was 25.8% [confidence interval (CI), 11.9-44.6]. The median progression-free survival was 2.69 months (95% CI, 1.91-2.99) and median overall survival was 7.85 months (95% CI, 4.47-not estimable). The most common treatment-related TEAE of any grade were neutropenia (77.4%), leukopenia (74.2%), and decreased appetite (51.6%). E7389-LF in combination with nivolumab significantly increased CD8-positive cells at C2D1 (P = 0.039), and six of seven vascular markers and four IFNγ-related markers showed increases from C1D1. CONCLUSIONS: Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with gastric cancer, and no new safety signals were observed, compared with either monotherapy.
Predictive and prognostic value of excision repair cross-complementing group 1 in patients with advanced gastric cancer 国際誌

Yasuhide Yamada, Kengo Nagashima, Mizutomo Azuma, Mitsuko Masutani, Hitoshi Ichikawa, Satoru Iwasa, Naoki Takahashi, Hidekazu Hirano, Keisuke Kanato, Nozomu Machida, Takahiro Kinoshita, Hiroaki Hata, Hisato Kawakami, Daisuke Takahari, Narikazu Boku, Yukinori Kurokawa, Masanori Terashima, Takaki Yoshikawa, Shigeki Sekine, Nobuyoshi Hiraoka

BJC Reports　2　(1)　18-18　2024年3月5日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1038/s44276-024-00046-w 　

eISSN：2731-9377

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Abstract Background To define the optimal chemotherapy regimen for each patient we therefore used tissue from patients to identify molecular prognostic or predictive biomarkers. Methods Endoscopic biopsy specimens from primary lesions and surgical specimens on a phase III trial in patients with unresectable advanced or recurrent gastric cancer treated with docetaxel with cisplatin plus S-1 (DCS) or cisplatin plus S-1 (CS), were collected. We measured the mRNA expression of ERCC1 and analyzed SNPs in GSTP1 and ERCC1. Results Low ERCC1 expression was associated with favorable prognosis for overall survival, OS by multivariable analysis (P = 0.001). There were significant interactions between the two treatment arms of DCS and CS, and ERCC1 mRNA expression. In patients with low ERCC1 expression of a favorable prognosis, DCS therapy was inferior to CS (P = 0.046). In addition to GSTP1 rs1695 (HR 1.728), ERCC1 rs3212980, ERCC1 rs2298881, ERCC1 rs3212964 with high expression of ERCC1 mRNA were associated with significantly worse prognosis with regard to OS. Conclusions ERCC1 mRNA is an independent prognostic factor and predictive marker that can be used to guide the addition of docetaxel. The SNPs of ERCC1 and GSTP1 could be also prognostic or predictive factors.
Trifluridine/Tipiracil Plus Bevacizumab for Vulnerable Patients With Pretreated Metastatic Colorectal Cancer: A Retrospective Study (WJOG14520G). 国際誌

Yosuke Kito, Hisato Kawakami, Seiichiro Mitani, Shinichi Nishina, Toshihiko Matsumoto, Takao Tsuzuki, Yudai Shinohara, Hozumi Shimokawa, Ryosuke Kumanishi, Takashi Ohta, Hiroo Katsuya, Takeshi Kawakami, Tomohiro Nishina, Hiroko Hasegawa, Kohei Akiyoshi, Yasutaka Chiba, Kentaro Yamazaki, Shuichi Hironaka, Kei Muro

The oncologist　29　(3)　e330-e336　2024年3月4日

DOI： 10.1093/oncolo/oyad296 　

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BACKGROUND: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab has shown clinical benefit for metastatic colorectal cancer (mCRC) refractory to standard therapy. However, few data have been available for patients with pretreated mCRC who are intolerant of intensive therapy (vulnerable). METHODS: We performed a multicenter retrospective study (WJOG14520G; TWILIGHT) of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC. Eligibility criteria included previous chemotherapy (although patients treated with all key cytotoxic agents, a fluoropyrimidine, oxaliplatin, and irinotecan, were excluded) and intolerance of full-dose combination therapy with oxaliplatin or irinotecan at the start of FTD/TPI plus bevacizumab. RESULTS: The median age of 93 evaluable patients was 79 years (range, 21-90). Intolerance of intensive therapy was attributable to an older age in 60 (65%) patients, serious concomitant disease in 24 (26%) patients, and a poor performance status in 19 (20%) patients. FTD/TPI plus bevacizumab was administered as second-line treatment in 74 (80%) patients and as third- or fourth-line treatment in 19 (20%) patients. The objective response rate was 4.9% (95% confidence interval [CI], 1.4%-12.2%), and the disease control rate was 67.9% (95% CI, 56.6%-77.8%). With a median follow-up time of 21.6 months, median overall survival and progression-free survival were 18.6 months (95% CI, 12.1-23.2) and 6.3 months (95% CI, 5.0-8.3), respectively. Neutropenia of grade ≥3 developed in 50 (54%) patients, whereas 2 (2%) patients experienced febrile neutropenia, and no treatment-related death was observed. CONCLUSION: Our data show the potential efficacy and acceptable safety profile of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC.
胃がんに対するニボルマブ単独療法における血中cell-free DNAの治療効果予測についての臨床的有用性の検討

稲垣千晶, 川上尚人, 前田大地, 坂井大介, 浦川真哉, 西田謙太郎, 工藤敏啓, 江口英利, 土岐祐一郎, 和田尚, 佐藤太郎

日本胃癌学会総会記事　96回　306-306　2024年2月
出版者・発行元： (一社)日本胃癌学会
Phase II study of S-1 plus docetaxel as first-line treatment for older patients with advanced gastric cancer (OGSG 0902).

Tomono Kawase, Hiroshi Imamura, Ryohei Kawabata, Jin Matsuyama, Kazuhiro Nishikawa, Kazuhiro Yanagihara, Kazuyoshi Yamamoto, Noriyuki Hoki, Junji Kawada, Hisato Kawakami, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

International journal of clinical oncology　29　(2)　134-141　2024年2月

DOI： 10.1007/s10147-023-02437-4 　

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BACKGROUND: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. METHODS: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1-14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. RESULTS: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). CONCLUSIONS: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer.
Phase II Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Small Cell Lung Cancer Cohort. 国際誌

Makoto Nishio, Shuji Murakami, Hisato Kawakami, Kyoichi Okishio, Motohiro Tamiya, Haruki Kobayashi, Daichi Fujimoto, Shunichi Sugawara, Toshiyuki Kozuki, Yuko Oya, Hiroki Izumi, Takayuki Shiroyama, Miyako Satouchi, Noboru Yamamoto, Shota Kaname, Daiko Matsuoka, Yohei Otake, Takao Takase, Taro Semba, Koichi Azuma

Cancer research communications　4　(1)　226-235　2024年1月29日

DOI： 10.1158/2767-9764.CRC-23-0313 　

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PURPOSE: E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase II part of this phase Ib/II study assessed the efficacy/safety of E7389-LF in combination with nivolumab in several disease cohorts; herein, we report results from the small cell lung cancer (SCLC) cohort. EXPERIMENTAL DESIGN: Patients with unresectable/measurable SCLC and disease progression with first-line platinum-based chemotherapy with/without an immune checkpoint inhibitor (ICI) were enrolled to receive E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously every 3 weeks. The primary objective of this part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory assessments included overall survival (OS) and biomarkers. RESULTS: Thirty-four patients were enrolled. By the data cut-off date (May 31, 2022), 29 (85.3%) had discontinued. Efficacy/biomarker analyses included 33 patients (1 had their diagnosis changed postenrollment); the ORR of E7389-LF plus nivolumab was 24.2% [95% confidence interval (CI): 11.1-42.3], the median PFS was 3.98 months (95% CI: 2.63-4.40), and, at a median follow-up of 10.6 months, the median OS was not reached (95% CI: not estimable). Notably, 27 of 33 patients (81.8%) had received an ICI as their prior first-line therapy. Treatment-related, treatment-emergent adverse events occurred in 97.1% (any grade) and 82.4% (grade ≥3) of enrolled patients; the most common event was neutropenia. Changes in vascular and immune-related plasma markers were observed. CONCLUSIONS: E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks showed notable antitumor activity as second-line therapy for SCLC; no new safety signals were observed compared with either agent as monotherapy. SIGNIFICANCE: This phase II part of a phase Ib/II study assessed liposomal eribulin (E7389-LF) plus nivolumab in 34 patients with pretreated SCLC; 8 of 33 evaluable patients (including 6/27 pretreated with ICIs) had objective responses. The combination was tolerable; increases in vasculature-related biomarkers tended to correlate with responses.
Exploratory Biomarker Analysis Using Plasma Angiogenesis-Related Factors and Cell-Free DNA in the TRUSTY Study: A Randomized, Phase II/III Study of Trifluridine/Tipiracil Plus Bevacizumab as Second-Line Treatment for Metastatic Colorectal Cancer 国際誌

Yu Sunakawa, Yasutoshi Kuboki, Jun Watanabe, Tetsuji Terazawa, Hisato Kawakami, Mitsuru Yokota, Masato Nakamura, Masahito Kotaka, Naotoshi Sugimoto, Hitoshi Ojima, Eiji Oki, Takeshi Kajiwara, Yoshiyuki Yamamoto, Yasushi Tsuji, Tadamichi Denda, Takao Tamura, Soichiro Ishihara, Hiroya Taniguchi, Takako Eguchi Nakajima, Satoshi Morita, Kuniaki Shirao, Naruhito Takenaka, Daisuke Ozawa, Takayuki Yoshino

Targeted Oncology　19　(1)　59-69　2024年1月9日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1007/s11523-023-01027-8 　

ISSN：1776-2596

eISSN：1776-260X

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BACKGROUND: The TRUSTY study evaluated the efficacy of second-line trifluridine/tipiracil (FTD/TPI) plus bevacizumab in metastatic colorectal cancer (mCRC). OBJECTIVE: This exploratory biomarker analysis of TRUSTY investigated the relationship between baseline plasma concentrations of angiogenesis-related factors and cell-free DNA (cfDNA), and the efficacy of FTD/TPI plus bevacizumab in patients with mCRC. PATIENTS AND METHODS: The disease control rate (DCR) and progression-free survival (PFS) were compared between baseline plasma samples of patients with high and low plasma concentrations (based on the median value) of angiogenesis-related factors. Correlations between cfDNA concentrations and PFS were assessed. RESULTS: Baseline characteristics (n = 65) were as follows: male/female, 35/30; median age, 64 (range 25-84) years; and RAS status wild-type/mutant, 29/36. Patients in the hepatocyte growth factor (HGF)-low and interleukin (IL)-8-low groups had a significantly higher DCR (risk ratio [95% confidence intervals {CIs}]) than patients in the HGF-high (1.83 [1.12-2.98]) and IL-8-high (1.70 [1.02-2.82]) groups. PFS (hazard ratio {HR} [95% CI]) was significantly longer in patients in the HGF-low (0.33 [0.14-0.79]), IL-8-low (0.31 [0.14-0.70]), IL-6-low (0.19 [0.07-0.50]), osteopontin-low (0.39 [0.17-0.88]), thrombospondin-2-low (0.42 [0.18-0.98]), and tissue inhibitor of metalloproteinase-1-low (0.26 [0.10-0.67]) groups versus those having corresponding high plasma concentrations of these angiogenesis-related factors. No correlation was observed between cfDNA concentration and PFS. CONCLUSION: Low baseline plasma concentrations of HGF and IL-8 may predict better DCR and PFS in patients with mCRC receiving FTD/TPI plus bevacizumab, however further studies are warranted. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031180122.
Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial

Shitara, K., Bang, Y.-J., Iwasa, S., Sugimoto, N., Ryu, M.-H., Sakai, D., Chung, H.C., Kawakami, H., Yabusaki, H., Sakamoto, Y., Nishina, T., Inaki, K., Kuwahara, Y., Wada, N., Suto, F., Arita, T., Sugihara, M., Tsuchihashi, Z., Saito, K., Kojima, A., Yamaguchi, K.

Nature Medicine　30　(7)　2024年

DOI： 10.1038/s41591-024-02992-x 　

ISSN：1546-170X 1078-8956
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer

Shitara, K., Fleitas, T., Kawakami, H., Curigliano, G., Narita, Y., Wang, F., Wardhani, S.O., Basade, M., Rha, S.Y., Wan, Zamaniah, W.I., Sacdalan, D.L., Ng, M., Yeh, K.H., Sunpaweravong, P., Sirachainan, E., Chen, M.-H., Yong, W.P., Peneyra, J.L., Ibtisam, M.N., Lee, K.-W., Krishna, V., Pribadi, R.R., Li, J., Lui, A., Yoshino, T., Baba, E., Nakayama, I., Pentheroudakis, G., Shoji, H., Cervantes, A., Ishioka, C., Smyth, E.

ESMO Open　9　(2)　2024年

DOI： 10.1016/j.esmoop.2023.102226 　

ISSN：2059-7029
Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial

Raghav, K., Siena, S., Takashima, A., Kato, T., Van den Eynde, M., Pietrantonio, F., Komatsu, Y., Kawakami, H., Peeters, M., Andre, T., Lonardi, S., Yamaguchi, K., Tie, J., Castro, C.G., Hsu, H.-C., Strickler, J.H., Kim, T.-Y., Cha, Y., Barrios, D., Yan, Q., Kamio, T., Kobayashi, K., Boran, A., Koga, M., Allard, J.D., Yoshino, T.

The Lancet Oncology　25　(9)　2024年

DOI： 10.1016/S1470-2045(24)00380-2 　

ISSN：1474-5488 1470-2045
Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study

Kawazoe, A., Xu, R.-H., Garc{\'i}a-Alfonso, P., Passhak, M., Teng, H.-W., Shergill, A., Gumus, M., Qvortrup, C., Stintzing, S., Towns, K., Kim, T.W., Shiu, K.K., Cundom, J., Ananda, S., Lebedinets, A., Fu, R., Jain, R., Adelberg, D., Heinemann, V., Yoshino, T., Elez, E., Cundom, J., Slutsky, E., Grasselli, J., Fein, L., Bella Quero, L., Joubert, W., Gibbs, P., Price, T., Burge, M., Ananda, S., Khattak, M., Colwell, B., Couture, F., Meyers, B., Towns, K., Sawyer, M., Sideris, L., Xu, R., Wang, W., Pan, H., Pfeiffer, P., Jensen, L.H., Qvortrup, C., Stintzing, S., Arnold, D., Lorenzen, S., Kubicka, S., Depenbusch, R., Passhak, M., Geva, R., Hubert, A., Shacham-Shmueli, E., Kornev, G., Kawazoe, A., Masuishi, T., Takashima, A., Hara, H., Kawakami, H., MacHida, N., Yamazaki, K., Yasui, H., Tsuji, A., Esaki, T., Yamaguchi, K., Kim, T.-Y., Ahn, J.B., Lee, M.A., Kim, T.W., Park, J.O., Lee, S., Orlova, R., Sarzhevskiy, V., Sekacheva, M., Tjulandin, S., Shirokova, O., Iskhakova, A., Lebedinets, A., Jimenez Fonseca, P., Rivera Herrero, F., Elez Fernandez, E., Garcia Alfonso, P., Gomez Reina, M.J., Yeh, K.-H., Teng, H.-W., Yang, T.S., Wang, H.-M., Yeh, Y.-M., Ozguroglu, M., Gumus, M., Yalcin, S., Erdogan, B., Demirci, U., Gursoy, P., Harputluoglu, H., Demir, A., Shiu, K.-K., Brown, E., Ross, P., Smyth, E., Chau, I., Saunders, M., Vaccaro, G., McCune, S., Wadlow, R., Khan, G., Bashir, B., Koontz, M., Martin, L., Shergill, A., Cobb, P., Kochenderfer, M.

Journal of Clinical Oncology　42　(24)　2024年

DOI： 10.1200/JCO.23.02736 　

ISSN：1527-7755 0732-183X
PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays

Klempner, S.J., Cowden, E.S., Cytryn, S.L., Fassan, M., Kawakami, H., Shimada, H., Tang, L.H., Wagner, D.-C., Yatabe, Y., Savchenko, A., Salcius, J., Johng, D., Chen, J., Montenegro, G., Moehler, M.

JCO Precision Oncology　8　2024年

DOI： 10.1200/PO.24.00230 　

ISSN：2473-4284
Real-World Treatment Sequencing in Vulnerable Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Study. 国際誌

Seiichiro Mitani, Yosuke Kito, Kaori Hino, Kentaro Kawakami, Naoki Izawa, Fumiyasu Hanamura, Yoshiyuki Yamamoto, Hirokazu Shoji, Azusa Komori, Shogen Boku, Kenji Tsuchihashi, Kyoko Kato, Yoshikane Nonagase, Toshihiko Matsumoto, Mitsuhiro Furuta, Hisato Kawakami

Targeted oncology　18　(5)　707-715　2023年9月5日

DOI： 10.1007/s11523-023-00996-0 　

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BACKGROUND: Data regarding treatment sequence for vulnerable patients with metastatic colorectal cancer (mCRC) in a real-world setting are lacking. OBJECTIVE: We aimed to assess treatment outcomes in second-line or later chemotherapy for vulnerable patients with mCRC in a real-world setting. PATIENTS AND METHODS: Vulnerable patients with mCRC who received less intensive treatment ('vulnerable') regimens, i.e. fluoropyrimidines with or without biologics (FP), reduced-dose doublet regimens with or without biologics (Doublet), and anti-epidermal growth factor receptor monotherapy (Anti-EGFR), as first-line therapy between June 2015 and December 2018 were retrospectively reviewed. RESULTS: A total of 210 patients from 15 hospitals were analyzed. The median age was 78 years (range 28-90), and 44 patients (21%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 2. In the entire population, the median time to treatment failure (TTF) and overall survival (OS) were 7.6 and 21.4 months, respectively. Following the failure of first-line therapy in 195 patients, 74 (38%), 24 (12%), and 13 (7%) patients received vulnerable regimens, full-dose doublet regimens with or without biologics, and other regimens, respectively, whereas 84 (43%) received best supportive care (BSC). In patients receiving vulnerable regimens as second-line therapy, the median TTF and OS were 4.4 and 13.7 months, respectively, while response rate and disease control rate were 18% and 62%, respectively. In 84 patients who received BSC, the median OS was 3.5 months. CONCLUSIONS: Second-line chemotherapy for vulnerable patients with mCRC showed clinically meaningful outcomes; however, few patients received second-line therapy, and survival among patients who received BSC was dismal.
Effect of the number of cycles of docetaxel + S-1 therapy on long-term survival in adjuvant chemotherapy for stage III gastric cancer. A pooled analysis of the OGSG0604 and OGSG1002 trials.

Yutaka Kimura, Hisato Kawakami, Shigeyuki Tamura, Kazumasa Fujitani, Jin Matsuyama, Hiroshi Imamura, Shohei Iijima, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Toshimasa Tsujinaka, Hiroshi Furukawa, Taroh Satoh

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　26　(5)　788-797　2023年9月

DOI： 10.1007/s10120-023-01408-y 　

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BACKGROUND: S-1 plus docetaxel (DS) therapy followed by S-1 is the standard of care in Japan in postoperative adjuvant chemotherapy for stage III gastric cancer, but long-term survival and the number of DS cycles required are unclear. The purpose of this study was to investigate the impact of the number of cycles of DS therapy on the 5-year survival in stage III gastric cancer in a pooled analysis of two phase II trials (OGSG0604 and OGSG1002). PATIENTS AND METHODS: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled in this pooled analysis. They received DS therapy for four or eight cycles, followed by S-1 until 1 year postgastrectomy. The 5-year overall survival (OS) and the 5-year disease free survival (DFS) by the landmark analysis was evaluated. RESULTS: In total, 113 patients from the OGSG0604 and OGSG1002 trials were enrolled in this study. The landmark analysis showed a 5-year OS that was better with four to eight cycles of DS therapy than with one to three cycles of DS therapy, with the best 5-year OS of 77.4% (95% confidence interval, 66.5-90.1%) for eight cycles. The 5-year DFS was approximately 66% when four or eight cycles of DS therapy were given. CONCLUSION: Although eight cycles of DS therapy may prolong prognosis, the present study did not provide a clear conclusion as to how many DS therapy cycles are needed to improve prognosis after D2 gastrectomy for stage III gastric cancer. TRIAL REGISTRATION: Registration number: UMIN00000714 and UMIN000004440.
Phase I dose-escalation study on irinotecan, cisplatin, and S-1 combination in chemotherapy-naïve patients with HER2-negative advanced gastric cancer (HERBIS-4B, OGSG 1106).

Hiroki Yukami, Hisato Kawakami, Toshifumi Yamaguchi, Daisuke Sakai, Toshio Shimokawa, Yukinori Kurokawa, Masahiro Goto, Taroh Satoh

International journal of clinical oncology　28　(9)　1176-1182　2023年9月

DOI： 10.1007/s10147-023-02376-0 　

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BACKGROUND: The development of triplet regimens for advanced gastric cancer is challenging. The aim of this phase I dose-escalation study was to determine the maximum tolerated dose and recommended dose of the combination of irinotecan, cisplatin, and S-1 in chemotherapy-naïve patients with HER2-negative advanced gastric cancer. METHODS: The 3 + 3 design was adopted. Every 4 weeks, patients received an escalating dose of intravenous irinotecan (100-150 mg/m2) on day 1 and fixed doses of intravenous cisplatin (60 mg/m2) on day 1 and oral S-1 (80 mg/m2) on days 1 to 14. RESULTS: Twelve patients were enrolled in two dose level cohorts. In the level 1 cohort (irinotecan 100 mg/m2, cisplatin 60 mg/m2, and S-1 80 mg/m2), dose-limiting toxicity including grade 4 neutropenia and febrile neutropenia occurred in one of six patients, whereas in the level 2 cohort (irinotecan 125 mg/m2, cisplatin 60 mg/m2, and S-1 80 mg/m2), dose-limiting toxicities including grade 4 neutropenia developed in two of six patients. Thus, the level 1 and 2 doses were determined to be the recommended and maximum tolerated doses, respectively. Common grade 3 or higher adverse events were neutropenia (75%; n = 9), anemia (25%; n = 3), anorexia (8%; n = 1), and febrile neutropenia (17%; n = 2). Irinotecan, cisplatin, and S-1 combination therapy achieved an overall response rate of 67% with a median progression-free survival and overall survival of 19.3 and 22.4 months, respectively. CONCLUSIONS: The potential treatment efficacy of this triplet regimen in HER2-negative advanced gastric cancer warrants further evaluation, especially in patients requiring intensive chemotherapy.
Role of plasma angiogenesis factors in the efficacy of first-line chemotherapy combined with biologics in RAS wild-type metastatic colorectal cancer: Results from the GI-SCREEN CRC-Ukit study. 国際誌

Satoshi Yuki, Kentaro Yamazaki, Yu Sunakawa, Hiroya Taniguchi, Hideaki Bando, Manabu Shiozawa, Tomohiro Nishina, Hisateru Yasui, Yoshinori Kagawa, Naoki Takahashi, Tadamichi Denda, Taito Esaki, Hisato Kawakami, Hironaga Satake, Atsuo Takashima, Nobuhisa Matsuhashi, Takeshi Kato, Chiharu Asano, Yukiko Abe, Shogo Nomura, Takayuki Yoshino

Cancer medicine　12　(18)　18702-18716　2023年8月28日

DOI： 10.1002/cam4.6486 　

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BACKGROUND: Several biomarkers have been established for metastatic colorectal cancer (mCRC). We investigated whether plasma angiogenesis factors could predict the efficacy of biologics combined with chemotherapy in first-line (1L) treatment in patients with RAS wild-type mCRC and the dynamics of plasma angiogenesis factors at progression during 1L treatment. METHODS: In this multicenter prospective observational study, serial plasma samples were prospectively collected at pretreatment and progression stages; 17 plasma angiogenesis factors were analyzed using the multiplex assay with Luminex® technology. Interactions between the pretreatment measurements and treatment groups on progression-free survival (PFS) and overall survival (OS) in patients with RAS wild-type were assessed using the propensity-score weighted Cox proportional hazards model. RESULTS: From February 2018 to September 2020, 202 patients were enrolled in the 1L cohort; 133 patients had RAS wild-type (chemotherapy plus bevacizumab [BEV group, n = 33] and plus anti-epidermal growth factor receptor monoclonal antibodies [aEGFR group, n = 100]). A trend of strong interaction on PFS was observed for interleukin-8 (IL-8) (p = 0.0752) and soluble vascular cell adhesion molecule-1 (sVCAM-1) (p = 0.0156). Regarding OS, IL-8 (p = 0.0283), soluble vascular endothelial growth factor-receptor-1 (sVEGFR-1) (p = 0.0777) and sVCAM-1 (p = 0.0011) tended to differentiate the treatment effect. In 112 patients, plasma samples were evaluable for dynamic analysis (57 and 55 from the BEV and aEGFR groups, respectively). In the BEV group, six factors significantly increased during progression, whereas two decreased. In the aEGFR group, three factors significantly increased, and six decreased. CONCLUSION: Pretreatment plasma IL-8 and sVCAM-1 levels could be predictive biomarkers to distinguish BEV and anti-EGFR mAbs when combined with chemotherapy in the 1L treatment of RAS wild-type mCRC. Several plasma angiogenesis factors showed significant change at progression in 1L chemotherapy plus biologics for RAS wild-type mCRC, which are potential biomarkers for selecting an optimal angiogenesis inhibitor in second-line treatment.
Meta-analysis of three randomized trials of capecitabine plus cisplatin (XP) versus S-1 plus cisplatin (SP) as first-line treatment for advanced gastric cancer.

Kazuhiro Nishikawa, Hisato Kawakami, Toshio Shimokawa, Kazumasa Fujitani, Shigeyuki Tamura, Shunji Endo, Michiya Kobayashi, Junji Kawada, Yukinori Kurokawa, Akira Tsuburaya, Takaki Yoshikawa, Junichi Sakamoto, Taroh Satoh

International journal of clinical oncology　28　(11)　1501-1510　2023年8月27日

DOI： 10.1007/s10147-023-02402-1 　

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BACKGROUND: S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) are standard first-line regimens for advanced gastric cancer (AGC) worldwide. We conducted a meta-analysis using individual participant data (IPD) to investigate which is more suitable. METHODS: IPD from three randomized trials were collected. In these trials, patients with AGC were randomly allocated to SP (S-1 80-120 mg for 21 days plus cisplatin 60 mg/m2 (q5w)) or XP (capecitabine 2000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w)). RESULTS: In 211 eligible patients, median overall survival (OS) for SP versus XP was 13.5 and 11.7 months (hazard ratio [HR], 0.787; p = 0.114), progression-free survival (PFS) was 6.2 and 5.1 months (HR, 0.767; P = 0.076), and TTF was 5.1 and 4.0 months (HR, 0.611; P = 0.001). The most common grade ≥ 3 adverse events with SP or XP were neutropenia (18% vs. 29%) and anorexia (16% vs.18%). Subgroup analysis demonstrated significant interaction between treatment effect and performance status > 1 (HR, 0.685; P = 0.036), measurable lesion (HR, 0.709; P = 0.049), primary upper third tumor (HR, 0.539; P = 0.040), and differentiated type (HR, 0.549; interaction, 0.236; P = 0.019). For the differentiated type, OS was significantly longer in the SP group (13.2 months) than in the XP group (11.1 months) (HR, 0.549; P = 0.019). For the undifferentiated type, OS was similar in the SP group (14.2 months) and in the XP group (12.4 months) (HR, 0.868; P = 0.476). CONCLUSIONS: SP and XP were both effective and well tolerated. SP might be suitable for the pathological differentiated subtype of AGC. CLINICAL TRIAL REGISTRATION: The HERBIS-2, HERBIS-4A, and XParTS II trials were registered with UMIN-CTR as UMIN000006105, UMIN000006755, and UMIN000006045, respectively.
Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G) 国際誌

Naoki Takahashi, Hiroki Hara, Kengo Nagashima, Kenro Hirata, Toshiki Masuishi, Toshihiko Matsumoto, Hisato Kawakami, Kentaro Yamazaki, Shuichi Hironaka, Narikazu Boku, Kei Muro

BMC Cancer　23　(1)　726-726　2023年8月5日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1186/s12885-023-11199-1 　

eISSN：1471-2407

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Abstract Background Trifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab (RAM) as third- or later-line treatments for advanced GC or EGJ cancer, there have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy. Therefore, we have started a randomised phase II trial to evaluate the efficacy and safety of FTD/TPI plus RAM compared with FTD/TPI monotherapy as third- or later-line treatments in patients with advanced GC and EGJ adenocarcinoma. Methods This RETREVE trial (WJOG15822G) is a prospective, open-label, randomised, multicentre phase II trial comparing FTD/TPI plus RAM versus FTD/TPI monotherapy in a third- or later-line setting. Eligibility criteria include age of > 20 years; performance status of 0 or 1; unresectable or recurrent gastric or EGJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. FTD/TPI (35 mg/m² twice daily, evening of day 1 to morning of day 6 and evening of day 8 to morning of day 13) was administered orally every 4 weeks, and RAM (8 mg/kg) was administered intravenously every 2 weeks. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, objective response rate, disease control rate, and safety. The expected hazard ratio of PFS is set as 0.7, assuming 4-month PFS rate of 27% in FTD/TPI monotherapy and 40% in FTD/TPI plus RAM. The number of subjects was 110, with a one-sided alpha error of 0.10 and power of 0.70. Discussion This study will clarify the additional effect of RAM continuation beyond disease progression on FTD/TPI in the third- or later-line setting for patients with advanced GC or EGJ cancer. Trial registration jRCTs041220120.
Mutational spectrum of TP53 gene correlates with nivolumab treatment efficacy in advanced gastric cancer (TP53MUT study). 国際誌

Koji Ando, Yoshiaki Nakamura, Hiroyuki Kitao, Mototsugu Shimokawa, Daisuke Kotani, Hideaki Bando, Tomohiro Nishina, Takanobu Yamada, Satoshi Yuki, Yukiya Narita, Hiroki Hara, Takashi Ohta, Taito Esaki, Yasuo Hamamoto, Ken Kato, Yoshiyuki Yamamoto, Keiko Minashi, Koushiro Ohtsubo, Naoki Izawa, Hisato Kawakami, Takeshi Kato, Taroh Satoh, Naohiro Okano, Akihito Tsuji, Kentaro Yamazaki, Takayuki Yoshino, Yoshihiko Maehara, Eiji Oki

British journal of cancer　129　(6)　1032-1039　2023年8月2日

DOI： 10.1038/s41416-023-02378-9 　

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BACKGROUND: Although nivolumab has a high efficacy, reliable biomarkers are needed to predict the efficacy. We evaluated the nivolumab efficacy according to the TP53 mutation in advanced gastric cancer patients enrolled in the GI-SCREEN project. METHODS: Sequence data of tumour specimens and clinicopathological information of 913 patients with advanced gastric cancer who were enrolled between April 2015 and March 2017 were obtained from the GI-SCREEN database. The follow-up information of 266 patients treated with nivolumab was also provided. RESULTS: Among 266 patients treated with nivolumab, the objective response rate (ORR) of TP53 wild type (wt) patients (24.6%) was higher than that of TP53 mutant patients (14.8%). Among TP53 mutant patients, the ORR of the frameshift type tended to be higher than the transition and transversion type (23.1%, 13.6%, and 13.0%, respectively). The median progression-free survival (PFS) was statistically longer in TP53 wt patients than in mutant patients (3.3 vs 2.1 months, HR 1.4, 95% CI 1.1-1.9). Among TP53 mutant patients, PFS was statistically longer in the frameshift type than in the transversion type. CONCLUSION: Nivolumab showed better efficacy in TP53 wt patients than in mutant patients. Among TP53 mutant patients, the frameshift type may have efficacy from nivolumab treatment.
The Phase II Study of Panitumumab in Chemotherapy-Naïve Frail or Elderly Patients with RAS Wild-type Colorectal Cancer: OGSG 1602 Final Results. 国際誌

Tetsuji Terazawa, Takeshi Kato, Masahiro Goto, Katsuya Ohta, Hironaga Satake, Shingo Noura, Yoshinori Kagawa, Hisato Kawakami, Hiroko Hasegawa, Kazuhiro Yanagihara, Tatsushi Shingai, Ken Nakata, Masahito Kotaka, Masayuki Hiraki, Ken Konishi, Shiro Nakae, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Toshimasa Tsujinaka, Taroh Satoh

The oncologist　28　(7)　e565-e574　2023年7月5日

DOI： 10.1093/oncolo/oyac145 　

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BACKGROUND: We previously reported the response rate of a phase II OGSG1602 study on panitumumab in chemotherapy-naive frail or elderly patients with RAS wild-type unresectable colorectal cancer (CRC) [Terazawa T, Kato T, Goto M, et al. Oncologist. 2021;26(1):17]. Herein, we report a survival analysis. METHODS: Patients aged ≥65 years and considered unsuitable for intensive chemotherapy or aged ≥76 years were enrolled. Primary tumors located from the cecum to the transverse colon were considered right-sided tumors (RSTs); those located from the splenic flexure to the rectum were considered left-sided tumors (LSTs). RESULTS: Among the 36 enrolled patients, 34 were included in the efficacy analysis, with 26 and 8 having LSTs and RSTs, respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.0 [95% CI, 5.4-10.0] and 17.5 months (95% CI, 13.8-24.3), respectively. Although no significant differences existed in PFS between patients with LST and RST {6.6 (95% CI, 5.4-11.5) vs. 4.9 months [95% CI, 1.9-not available (NA), P = .120]}, there were significant differences in OS [19.3 (95% CI, 14.2-NA) vs.12.3 months (95% CI, 9.9-NA), P = .043]. CONCLUSION: Panitumumab showed favorable OS in frail or elderly patients with RAS wild-type CRC and no prior exposure to chemotherapy. Panitumumab may be optimal for patients with LSTs (UMIN Clinical Trials Registry Number UMIN000024528).
Survival impact of microsatellite instability in stage II gastric cancer patients who received S-1 adjuvant monotherapy after curative resection. 国際誌

Chihiro Sato, Hisato Kawakami, Ryo Tanaka, Hironaga Satake, Kentaro Inoue, Yutaka Kimura, Junya Fujita, Ryohei Kawabata, Yasutaka Chiba, Taroh Satoh, Kazuhiko Nakagawa

Scientific reports　13　(1)　10826-10826　2023年7月4日

DOI： 10.1038/s41598-023-37870-y 　

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Adjuvant S-1 monotherapy is the standard of care for stage II gastric cancer (GC) after curative resection in Japan, but its efficacy for microsatellite instability-high (MSI-H) tumors has remained unknown. Among a multi-institutional cohort of patients with stage II GC who underwent R0 resection followed by S-1 adjuvant chemotherapy between February 2008 and December 2018, we assessed MSI status with an MSI-IVD Kit (Falco). MSI status was assessable for 184 (88.5%) of the 208 enrolled patients, with MSI-H being identified in 24 (13.0%) individuals. Although neither relapse-free survival (RFS) (hazard ratio [HR] = 1.00, p = 0.997) nor overall survival (OS) (HR = 0.66, p = 0.488) differed between MSI-H versus microsatellite-stable (MSS) patients, MSI-H patients showed a nonsignificant but better RFS (HR = 0.34, p = 0.064) and OS (HR = 0.22, p = 0.057) than did MSS patients after adjustment for background characteristics by propensity score (PS) analysis. Gene expression analysis in the PS-matched cohort suggested that recurrence was associated with the immunosuppressive microenvironment in MSI-H tumors but with expression of cancer/testis antigen genes in MSS tumors. Our data reveal a better adjusted survival for MSI-H versus MSS stage II GC treated with S-1 adjuvant therapy, and they suggest that mechanisms of recurrence differ between MSI-H and MSS tumors.
Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. 国際誌

Takayuki Yoshino, Maria Di Bartolomeo, Kanwal Raghav, Toshiki Masuishi, Fotios Loupakis, Hisato Kawakami, Kensei Yamaguchi, Tomohiro Nishina, Zev Wainberg, Elena Elez, Javier Rodriguez, Marwan Fakih, Fortunato Ciardiello, Kapil Saxena, Kojiro Kobayashi, Emarjola Bako, Yasuyuki Okuda, Gerold Meinhardt, Axel Grothey, Salvatore Siena

Nature communications　14　(1)　3332-3332　2023年6月7日

DOI： 10.1038/s41467-023-38032-4 　

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DESTINY-CRC01 (NCT03384940) was a multicenter, open-label, phase 2 trial assessing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-expressing metastatic colorectal cancer (mCRC) that progressed after ≥2 prior regimens; results of the primary analysis are published. Patients received T-DXd 6.4 mg/kg every 3 weeks and were assigned to either: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+), cohort B (IHC 2+/ISH-), or cohort C (IHC 1+). Primary endpoint was objective response rate (ORR) by independent central review in cohort A. Secondary endpoints included ORR (cohorts B and C), duration of response, disease control rate, progression-free survival, overall survival, pharmacokinetics, and safety of T-DXd. 86 patients were enrolled (53 in cohort A, 15 in cohort B, and 18 in cohort C). Results of the primary analysis are published, reporting an ORR of 45.3% in cohort A. Here, we report the final results. No responses occurred in cohorts B or C. Median progression-free survival, overall survival, and duration of response were 6.9, 15.5, and 7.0 months, respectively. Overall serum exposure (cycle 1) of T-DXd, total anti-HER2 antibody, and DXd were similar regardless of HER2 status. Most common grade ≥3 treatment-emergent adverse events were decreased neutrophil count and anemia. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 patients (9.3%). These findings support the continued exploration of T-DXd in HER2-positive mCRC.
Efficacy and safety of maintenance therapy with pamiparib versus placebo for advanced gastric cancer responding to first-line platinum-based chemotherapy: Phase 2 study results. 国際誌

Fortunato Ciardiello, Yung-Jue Bang, Andrés Cervantes, Mikhail Dvorkin, Charles D Lopez, Jean-Philippe Metges, Antonio Sánchez Ruiz, Mariona Calvo, Andrew H Strickland, George Kannourakis, Kei Muro, Hisato Kawakami, Jia Wei, Christophe Borg, Zhaoyin Zhu, Neal Gupta, Robert J Pelham, Lin Shen

Cancer medicine　12　(12)　13145-13154　2023年6月

DOI： 10.1002/cam4.5997 　

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BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved for the treatment of various solid tumors. In gastric cancer, genes commonly harbor mutations in the homologous recombination DNA repair pathway, potentially increasing sensitivity to PARPi. Pamiparib (BGB-290) is a small molecule inhibitor of PARP1 and PARP2. METHODS: The PARALLEL-303 study (NCT03427814) investigated the efficacy and safety of pamiparib 60 mg orally (PO) twice daily (BID) versus placebo PO BID as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line chemotherapy. The primary endpoint of this double-blind, randomized, global phase 2 study was progression-free survival (PFS) (RECIST version 1.1; per investigator assessment). Secondary endpoints included overall survival (OS) and safety. RESULTS: In total, 136 patients were randomized 1:1 to receive pamiparib (n = 71) or placebo (n = 65). Median PFS was numerically longer with pamiparib versus placebo but did not reach statistical significance (3.7 months [95% confidence interval (CI): 1.9, 5.3] vs. 2.1 months [95% CI: 1.9, 3.8]; hazard ratio 0.8 [95% CI: 0.5, 1.2]; p = 0.1428). Median OS was 10.2 months (95% CI: 8.7, 16.3) in the pamiparib arm versus 12.0 months (95% CI: 8.2, not estimable) in the placebo arm. Overall, 8 patients (11.3%) in the pamiparib arm and 2 patients (3.1%) in the placebo arm experienced ≥1 TEAE leading to treatment discontinuation. CONCLUSIONS: Maintenance pamiparib did not meet statistical significance for superiority versus placebo for PFS, but was well tolerated with few treatment discontinuations; no unexpected safety signals were identified.
A Phase II Trial of Trifluridine/Tipiracil in Combination with Cetuximab Rechallenge in Patients with RAS Wild-Type mCRC Refractory to Prior Anti-EGFR Antibodies: WJOG8916G Trial 国際誌

Naoki Izawa, Toshiki Masuishi, Naoki Takahashi, Hirokazu Shoji, Yoshiyuki Yamamoto, Toshihiko Matsumoto, Keiji Sugiyama, Takeshi Kajiwara, Kentaro Kawakami, Naoki Aomatsu, Chihiro Kondoh, Hisato Kawakami, Naoki Takegawa, Taito Esaki, Mototsugu Shimokawa, Kazuto Nishio, Yukiya Narita, Hiroki Hara, Yu Sunakawa, Narikazu Boku, Toshikazu Moriwaki, Takako Eguchi Nakajima, Kei Muro

Targeted Oncology　18　(3)　369-381　2023年5月6日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1007/s11523-023-00963-9 　

ISSN：1776-2596

eISSN：1776-260X

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BACKGROUND: Trifluridine/tipiracil (FTD/TPI) improved the overall survival in patients with metastatic colorectal cancer (mCRC) who had previously received standard chemotherapies; however, the clinical outcomes remain poor. OBJECTIVE: A multicenter phase II study aimed to assess the efficacy and safety of FTD/TPI plus cetuximab rechallenge. PATIENTS AND METHODS: Patients with histologically confirmed RAS wild-type mCRC refractory to prior anti-epidermal growth factor receptor (anti-EGFR) antibody were enrolled and treated with FTD/TPI (35 mg/m2 twice daily on days 1-5 and 8-12) plus cetuximab (initially 400 mg/m2, followed by weekly 250 mg/m2) every 4 weeks. The primary endpoint was disease control rate (DCR), expecting a target DCR of 65% and null hypothesis of 45% with 90% power and 10% one-sided alpha error. Gene alterations of RAS, BRAF, EGFR, PIK3CA, ERBB2, and MET in pre-treatment circulating tumor DNA were evaluated using the Guardant360 assay. RESULTS: A total of 56 patients (median age 60 years; left-sided tumors 91%; objective partial or complete response during the prior anti-EGFR therapy 61%) were enrolled. The DCR was 54% (80% confidence interval [CI] 44-63; P = 0.12), with a partial response rate of 3.6%. Median progression-free survival (PFS) was 2.4 months (95% CI 2.1-3.7). In the circulating tumor DNA analysis, patients without any alterations of the six genes (n = 20) demonstrated higher DCR (75% vs. 39%; P = 0.02) and longer PFS (median 4.7 vs. 2.1 months; P < 0.01) than those with any gene alterations (n = 33). The most common grade 3/4 hematologic adverse event was neutropenia (55%). No treatment-related deaths occurred. CONCLUSIONS: FTD/TPI plus cetuximab rechallenge did not demonstrate clinically meaningful efficacy in all mCRC patients, but might be beneficial for the molecularly selected population.
Soluble programmed cell death ligand 1 predicts prognosis for gastric cancer patients treated with nivolumab: Blood-based biomarker analysis for the DELIVER trial 国際誌

Hisato Kawakami, Yu Sunakawa, Eisuke Inoue, Ryo Matoba, Kenta Noda, Toshiyuki Sato, Chihiro Suminaka, Mami Yamaki, Yasuhiro Sakamoto, Ryohei Kawabata, Atsushi Ishiguro, Yusuke Akamaru, Yosuke Kito, Hiroshi Yabusaki, Jin Matsuyama, Masazumi Takahashi, Akitaka Makiyama, Hidetoshi Hayashi, Kenji Chamoto, Tasuku Honjo, Kazuhiko Nakagawa, Wataru Ichikawa, Masashi Fujii

European Journal of Cancer　184　10-20　2023年5月

DOI： 10.1016/j.ejca.2023.02.003 　

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BACKGROUND: The clinical value of soluble forms of programmed cell death-1 (sPD-1), PD ligand 1 (sPD-L1) and cytotoxic T lymphocyte-associated protein-4 (sCTLA-4) for gastric cancer (GC) patients treated with nivolumab monotherapy has remained unknown. METHODS: Blood samples collected before nivolumab treatment from 439 GC patients enrolled in the DELIVER (Japan Clinical Cancer Research Organisation GC-08) trial were analysed for sPD-1, sPD-L1 and sCTLA-4. Corresponding baseline clinical data were also retrieved. RESULTS: Higher plasma levels of sPD-1 (hazard ratio [HR] = 1.27, p = 0.020), sPD-L1 (HR = 1.86, p < 0.001) and sCTLA-4 (HR = 1.33, p = 0.008) were significantly associated with shorter overall survival (OS), whereas only higher sPD-L1 levels was significantly associated with shorter progression-free survival (HR = 1.30, p = 0.008). The sPD-L1 concentration was significantly associated with the Glasgow prognostic score (GPS) (p < 0.001), but both sPD-L1 (HR = 1.67, p < 0.001) and GPS (HR = 1.39, p = 0.009 for GPS 0 versus 1; HR = 1.95, p < 0.001 for GPS 0 versus 2) were independently associated with OS. Patients with a GPS of 0 and low sPD-L1 thus showed the longest OS (median, 12.0 months) and those with a GPS of 2 and high sPD-L1 showed the shortest OS (median, 3.1 months), yielding a HR of 3.69 (p < 0.001). CONCLUSION: Baseline sPD-L1 levels have the potential to predict survival for advanced GC patients treated with nivolumab, with the prognostic accuracy of sPD-L1 being improved by its combination with GPS.
Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer. 国際誌

Kei Muro, Kohei Shitara, Kensei Yamaguchi, Takaki Yoshikawa, Hironaga Satake, Hiroki Hara, Naotoshi Sugimoto, Nozomu Machida, Masahiro Goto, Hisato Kawakami, Kenji Amagai, Yasushi Omuro, Taito Esaki, Shuichi Hironaka, Tomohiro Nishina, Yoshito Komatsu, Hisahiro Matsubara, Shinichi Shiratori, Shirong Han, Taroh Satoh, Atsushi Ohtsu

Journal of gastrointestinal cancer　54　(3)　951-961　2023年4月10日

DOI： 10.1007/s12029-023-00920-9 　

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PURPOSE: Pembrolizumab demonstrated antitumor activity in programmed death ligand 1 positive (combined positive score (CPS) ≥ 1) gastric/gastroesophageal junction cancer in KEYNOTE-059 (third line or beyond), KEYNOTE-061 (second line), and KEYNOTE-062 (first line). We characterized efficacy and safety of pembrolizumab monotherapy in Japanese patients across several lines of therapy in these studies. METHODS: This analysis was conducted in 34 patients from KEYNOTE-059 cohort 1 (all pembrolizumab), including 13 patients with CPS ≥ 1, 65 patients with CPS ≥ 1 from KEYNOTE-061 (pembrolizumab, n = 27; chemotherapy, n = 38), and 70 patients with CPS ≥ 1 from KEYNOTE-062 (pembrolizumab, n = 38; chemotherapy, n = 32). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were evaluated. RESULTS: In KEYNOTE-059, ORR with pembrolizumab was 9%, median PFS was 2 months, and median OS was 10 months. In KEYNOTE-061, median OS was 12 months with pembrolizumab versus 10 months with chemotherapy (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.39-1.15). Median PFS (pembrolizumab vs. chemotherapy) was 2 months versus 4 months (HR, 1.21; 95% CI, 0.69-2.13); ORR was 7% versus 18%. In KEYNOTE-062, median OS was 20 months with pembrolizumab versus 18 months with chemotherapy (HR, 0.76; 95% CI, 0.43-1.33). Median PFS (pembrolizumab vs. chemotherapy) was 6 months versus 7 months (HR, 1.03; 95% CI, 0.61-1.74); ORR was 29% versus 34%. CONCLUSIONS: The current analysis provides valuable information that anti-PD-1 therapies are worthy of further assessment for gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02335411 (KEYNOTE-059), NCT02370498 (KEYNOTE-061), and NCT02494583 (KEYNOTE-062).
The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy. 国際誌

Chiaki Inagaki, Hisato Kawakami, Daichi Maeda, Daisuke Sakai, Shinya Urakawa, Kentaro Nishida, Toshihiro Kudo, Yuichiro Doki, Hidetoshi Eguchi, Hisashi Wada, Taroh Satoh

Scientific reports　13　(1)　5652-5652　2023年4月6日

DOI： 10.1038/s41598-023-32645-x 　

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To assess the potential clinical utility of cell-free DNA (cfDNA)-based biomarkers for identifying gastric cancer (GC) patients who benefit from nivolumab. From 31 GC patients treated with nivolumab monotherapy (240 mg/body, Bi-weekly) in 3rd or later line setting, we prospectively collected blood samples at baseline and before the 3rd dose. We compared cfDNA-based molecular findings, including microsatellite instability (MSI) status, to tissue-based biomarkers. We assessed the clinical value of blood tumor mutation burden (bTMB) and copy number alterations (CNA) as well as the cfDNA dynamics. The concordance between deficient-MMR and cfDNA-based MSI-high was 100% (3/3). Patients with bTMB ≥ 6 mut/Mb had significantly better progression-free survival (PFS) and overall survival (OS); however, such significance disappeared when excluding MSI-High cases. The combination of bTMB and CNA positivity identified patients with survival benefit regardless of MSI status (both PFS and OS, P < 0.001), with the best survival in those with bTMB≥6mut/Mb and CNAnegative. Moreover, patients with decreased bTMB during treatment had a better disease control rate (P = 0.04) and longer PFS (P = 0.04). Our results suggest that a combination of bTMB and CNA may predict nivolumab efficacy for GC patients regardless of MSI status. bTMB dynamics have a potential utility as an on-treatment biomarker.
Trifluridine/tipiracil+bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+BEV as second-line therapy for metastatic colorectal cancer: a randomised noninferiority trial 国際誌

Yasutoshi Kuboki, Tetsuji Terazawa, Toshiki Masuishi, Masato Nakamura, Jun Watanabe, Hitoshi Ojima, Akitaka Makiyama, Masahito Kotaka, Hiroki Hara, Yoshinori Kagawa, Naotoshi Sugimoto, Hisato Kawakami, Atsuo Takashima, Takeshi Kajiwara, Eiji Oki, Yu Sunakawa, Soichiro Ishihara, Hiroya Taniguchi, Takako Eguchi Nakajima, Satoshi Morita, Kuniaki Shirao, Naruhito Takenaka, Daisuke Ozawa, Takayuki Yoshino

British Journal of Cancer　128　(10)　1897-1905　2023年3月4日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1038/s41416-023-02212-2 　

ISSN：0007-0920

eISSN：1532-1827

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Abstract Background This open-label, multicentre, phase II/III trial assessed the noninferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab vs. fluoropyrimidine and irinotecan plus bevacizumab (control) as second-line treatment for metastatic colorectal cancer (mCRC). Methods Patients were randomised (1:1) to receive FTD/TPI (35 mg/m² twice daily, days 1–5 and days 8–12, 28-day cycle) plus bevacizumab (5 mg/kg, days 1 and 15) or control. The primary endpoint was overall survival (OS). The noninferiority margin of the hazard ratio (HR) was set to 1.33. Results Overall, 397 patients were enrolled. Baseline characteristics were similar between the groups. Median OS was 14.8 vs. 18.1 months (FTD/TPI plus bevacizumab vs. control; HR 1.38; 95% confidence interval [CI] 0.99–1.93; P_{noninferiority} = 0.5920). In patients with a baseline sum of the diameter of target lesions of <60 mm (n = 216, post hoc analyses), the adjusted median OS was similar between groups (FTD/TPI plus bevacizumab vs. control, 21.4 vs. 20.7 months; HR 0.92; 95% CI 0.55–1.55). Grade ≥3 adverse events (FTD/TPI plus bevacizumab vs. control) included neutropenia (65.8% vs. 41.6%) and diarrhoea (1.5% vs. 7.1%). Conclusions FTD/TPI plus bevacizumab did not demonstrate noninferiority to fluoropyrimidine and irinotecan plus bevacizumab as second-line treatment for mCRC. Clinical trial registration JapicCTI-173618, jRCTs031180122.
Efficacy of Targeted Trials and Signaling Pathway Landscape in Advanced Gastrointestinal Cancers From SCRUM-Japan GI-SCREEN: A Nationwide Genomic Profiling Program. 国際誌

Yoshiaki Nakamura, Riu Yamashita, Wataru Okamoto, Yoshito Komatsu, Satoshi Yuki, Makoto Ueno, Ken Kato, Hiroya Taniguchi, Yoshinori Kagawa, Tadamichi Denda, Hiroki Hara, Taito Esaki, Toshikazu Moriwaki, Yu Sunakawa, Eiji Oki, Fumio Nagashima, Tomohiro Nishina, Taroh Satoh, Hisato Kawakami, Kensei Yamaguchi, Koushiro Ohtsubo, Takeshi Kato, Yosuke Horita, Akihito Tsuji, Hisateru Yasui, Masahiro Goto, Yasuo Hamamoto, Masashi Wakabayashi, Takashi Ikeno, Kohei Shitara, Hideaki Bando, Katsuya Tsuchihara, Izumi Miki, Hiroko Ichiki, Atsushi Ohtsu, Takayuki Yoshino

JCO precision oncology　7　e2200653　2023年3月

DOI： 10.1200/PO.22.00653 　

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PURPOSE: Genomic profiling programs have been implemented to apply next-generation sequencing (NGS) for facilitating trial enrollment. SCRUM-Japan GI-SCREEN is a large-scale genomic profiling program in advanced gastrointestinal cancers using a validated genomic assay with the goal of facilitating enrollment in targeted clinical trials, generating real-world data, and performing clinicogenomic analysis for biomarker discovery. PATIENTS AND METHODS: Genotyping of tumor tissue samples from 5,743 patients with advanced gastrointestinal cancers enrolled in GI-SCREEN was centrally performed with NGS. Patients were enrolled in matched trials of targeted agents affiliated with GI-SCREEN on the basis of genotyping results. RESULTS: A total of 11 gastrointestinal cancers were included, with colorectal cancer being the most common. The median age ranged from 59 to 70.5 years across cancer types. Patients enrolled after initiation of first-line treatment had significantly longer overall survival (OS) than that before treatment initiation with a median survival time difference of 8.9 months and a hazard ratio (HR) ranging from 0.25 to 0.73 across cancer types, demonstrating an immortal time bias. One hundred and forty-nine patients received matched therapies in clinical trials on the basis of their identified alterations. Among patients with colorectal cancer harboring actionable alterations, the median OS was significantly longer in patients who received matched therapies in trials than in those who did not (HR, 0.52; 95% CI, 0.26 to 1.01; P = .049). Cancer-specific pathway alterations were significantly associated with shorter survival and related to primary resistance to matched trial therapies. CONCLUSION: Our genomic profiling program led to patient enrollment in targeted clinical trials and improved survival of patients with colorectal cancer who received matched therapies in clinical trials. To avoid immortal time bias, precautions are needed when using data from patients who have undergone NGS testing after initiation of the evaluated treatment line.
Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. 国際誌

Kensei Yamaguchi, Yung-Jue Bang, Satoru Iwasa, Naotoshi Sugimoto, Min-Hee Ryu, Daisuke Sakai, Hyun Cheol Chung, Hisato Kawakami, Hiroshi Yabusaki, Jeeyun Lee, Tatsu Shimoyama, Keun-Wook Lee, Kaku Saito, Yoshinori Kawaguchi, Takahiro Kamio, Akihito Kojima, Masahiro Sugihara, Kohei Shitara

Journal of clinical oncology : official journal of the American Society of Clinical Oncology　41　(4)　816-825　2023年2月1日

DOI： 10.1200/JCO.22.00575 　

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PURPOSE: To investigate efficacy and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-low gastric or gastroesophageal junction (GEJ) adenocarcinoma. METHODS: Patients with locally advanced or metastatic HER2-low (cohort 1, immunohistochemistry 2+/in situ hybridization-negative; cohort 2, immunohistochemistry 1+) gastric/GEJ adenocarcinoma treated with at least two prior regimens, including fluoropyrimidine and platinum, but anti-HER2 therapy naive, received T-DXd 6.4 mg/kg intravenously once every 3 weeks. The primary end point was confirmed objective response rate by independent central review. RESULTS: Among 21 patients enrolled in cohort 1 and 24 enrolled in cohort 2, 19 and 21 patients, respectively, had central HER2 confirmation, received T-DXd, and had measurable tumors at baseline. The confirmed objective response rate was 26.3% (95% CI, 9.1 to 51.2) from five partial responses in cohort 1 and 9.5% (95% CI, 1.2 to 30.4) from two partial responses in cohort 2. Thirteen patients (68.4%) in cohort 1 and 12 (60.0%) in cohort 2 experienced reduced tumor size. The median overall survival was 7.8 months (95% CI, 4.7 to nonevaluable) in cohort 1 and 8.5 months (95% CI, 4.3 to 10.9) in cohort 2; the median progression-free survival was 4.4 months (95% CI, 2.7 to 7.1) and 2.8 months (95% CI, 1.5 to 4.3), respectively. The most common grade ≥ 3 treatment-emergent adverse events in cohorts 1 and 2 were anemia (30.0% and 29.2%), decreased neutrophil count (25.0% and 29.2%), and decreased appetite (20.0% and 20.8%). Drug-related interstitial lung disease/pneumonitis occurred in one patient in each cohort (grade 1 or 2). No drug-related deaths occurred. CONCLUSION: This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/GEJ adenocarcinoma.
Correction: Implication of changes in PD-L1 expression during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen in esophageal squamous cell carcinoma.

Seiichiro Mitani, Hisato Kawakami, Osamu Shiraishi, Hiroaki Kanemura, Shinichiro Suzuki, Koji Haratani, Hidetoshi Hayashi, Kimio Yonesaka, Yasutaka Chiba, Takushi Yasuda, Kazuhiko Nakagawa

Esophagus : official journal of the Japan Esophageal Society　20　(2)　290-290　2023年1月20日

DOI： 10.1007/s10388-023-00986-1 　
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial

Rha, S.Y., Oh, D.-Y., Ya{\~n}ez, P., Bai, Y., Ryu, M.-H., Lee, J., Rivera, F., Alves, G.V., Garrido, M., Shiu, K.-K., Fern{\'a}ndez, M.G., Li, J., Lowery, M.A., ?il, T., Cruz, F.M., Qin, S., Luo, S., Pan, H., Wainberg, Z.A., Yin, L., Bordia, S., Bhagia, P., Wyrwicz, L.S., Mendez, G., O{'}Connor, J.M., Yanzi Castilla, A., Cundom, J., Kaen, D., Wong, R., Ng, W., Aghmesheh, M., Peressoni, M., Andrade, C., Franke, F., Alves, G., Cruz, F.J., Vianna, K., Monteiro, M.M., Raphael, M., Berry, S., Jang, R., Tan, A., Asselah, J., Yanez Weber, P., Mahave, M., Sanchez, C., Salman, P., Zhang, X., Liu, T., Lin, X., Yang, J., Li, W., Ying, J., Chen, X., Zeng, S., Qu, Y., Yang, L., Zhao, L., Chen, P., Li, E., Ye, F., Lu, J., Liang, X., Zhao, Q., Yin, X., Li, J., Ling, Y., Lv, G., Li, S., Guerrero, A., Rubiano, J., Gonzalez Fernandez, M., Manneh Kopp, R., Guzman Ramirez, A., Corrales, L., Gonzalez Herrera, I., Melichar, B., Buchler, T., Svoboda, T., Obermannova, R., Vrana, D., Cvek, J., Pfeiffer, P., Baeksgaard, L., Yilmaz, M., Boige, V., Lopez-Trabada, D., Borg, C., Pannier, D., Hiret, S., Di Fiore, F., Metges, J.-P., Arnold, D., Martens, U., Lordick, F., Stein, A., Castro, H., Lopez, K., Ramirez, J., Aguilar, M., Chivalan, M., Chan, W., Cheng, A., Yeo, W., Arkosy, P., Csoszi, T., Hitre, E., Horvath, Z., Lowery, M., McDermott, R., Morris, P., Hubert, A., Brenner, B., Ben-Aharon, I., Shacham-Shmueli, E., Man, S., Pelles Avraham, S., Brenner, R., Mishaeli, M., Di Bartolomeo, M., Fazio, N., Lonardi, S., Garufi, C., Satoh, T., Hara, H., Iwagami, S., Yasui, H., Tsuda, M., Shimoyama, T., Shoji, H., Sugimoto, N., Shibata, N., Yamaguchi, K., Amagai, K., Choda, Y., Esaki, T., Yabusaki, H., Oshima, T., Tsuji, A., Kawakami, H., Kawazoe, A., Ishido, K., Kadowaki, S., Martinez Rodriguez, J., Herrera Martinez, M., Huitzil Melendez, F., Ramirez Godinez, F., Balancan, P., Damianovich, D., Castro Oliden, V., Grados, J., Torres, C., Wyrwicz, L., Wysocki, P., Hajac, L., Zolnierek, J., Karaszewska, B., Orlova, R., Tjulandin, S., Fadeeva, N., Makarycheva, Y., Nosov, D., Smagina, M., Chan, S., Jacobs, C., Kraus, P., Landers, G., Robertson, B., Ruff, P., Schoeman, E., Maurel, J.-M., Diez Garcia, M., Jimenez Fonseca, P., Gallego Plazas, J., Rivera Herrero, F., Miranda Poma, J., Layos Romero, L., Fritsch, R., Bastian, S., Winterhalder, R., Dosso, S.D., Kossler, T., d Yeh, K.-H., Yen, C.-J., Chen, Y.-Y., Lin, J., Bilici, M., Ozguroglu, M., Cil, T., Oksuzoglu, B., Harputluoglu, H., Karaoglu, A., Hacibekiroglu, I., Erdogan, B., Yalcin, S., Adamchuk, H., Bondarenko, I., Kolesnik, O., Ostapenko, Y., Kryzhanivska, A., Leshchenko, L., Ilin, I., Shparyk, Y., Trukhin, D., Voitko, N., Roy, R., Young, A.-M., Medley, L., Celano, P., Overton, L., Raj, M., Dunne, R., Wainberg, Z., Dayyani, F., Larson, T., Kochenderfer, M.

The Lancet Oncology　24　(11)　2023年

DOI： 10.1016/S1470-2045(23)00515-6 　

ISSN：1474-5488 1470-2045
The combination of soluble forms of PD-1 and PD-L1 as a predictive marker of PD-1 blockade in patients with advanced cancers: a multicenter retrospective study. 国際誌

Takashi Kurosaki, Kenji Chamoto, Shinichiro Suzuki, Hiroaki Kanemura, Seiichiro Mitani, Kaoru Tanaka, Hisato Kawakami, Yo Kishimoto, Yasuharu Haku, Katsuhiro Ito, Toshiyuki Sato, Chihiro Suminaka, Mami Yamaki, Yasutaka Chiba, Tomonori Yaguchi, Koichi Omori, Takashi Kobayashi, Kazuhiko Nakagawa, Tasuku Honjo, Hidetoshi Hayashi

Frontiers in immunology　14　1325462-1325462　2023年

DOI： 10.3389/fimmu.2023.1325462 　

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INTRODUCTION: The clinical relevance of soluble forms of programmed cell death-1 (sPD-1) and programmed cell death-ligand 1 (sPD-L1) remains unclear. We here investigated the relation between the efficacy of PD-1 blockade and pretreatment plasma levels of sPD-1 and sPD-L1 across a broad range of cancer types. METHODS: We retrospectively analyzed clinical data from 171 patients with advanced solid tumors who received nivolumab or pembrolizumab monotherapy regardless of treatment line. The concentrations of sPD-1 and sPD-L1 were measured with a fully automated immunoassay (HISCL system). RESULTS: The study subjects comprised patients with head and neck cancer (n = 50), urothelial cancer (n = 42), renal cell cancer (n = 37), gastric cancer (n = 20), esophageal cancer (n = 10), malignant pleural mesothelioma (n = 6), or microsatellite instability-high tumors (n = 6). High or low levels of sPD-1 or sPD-L1 were not significantly associated with progression-free survival (PFS) or overall survival (OS) for PD-1 blockade in the entire study population. Comparison of treatment outcomes according to combinations of high or low sPD-1 and sPD-L1 levels, however, revealed that patients with low sPD-1 and high sPD-L1 concentrations had a significantly poorer PFS (HR of 1.79 [95% CI, 1.13-2.83], p = 0.01) and a tendency toward poorer OS (HR of 1.70 [95% CI, 0.99-2.91], p = 0.05) compared with all other patients. CONCLUSION: Our findings suggest that the combination of low sPD-1 and high sPD-L1 levels is a potential negative biomarker for PD-1 blockade therapy.
Implication of changes in PD-L1 expression during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen in esophageal squamous cell carcinoma.

Seiichiro Mitani, Hisato Kawakami, Osamu Shiraishi, Hiroaki Kanemura, Shinichiro Suzuki, Koji Haratani, Hidetoshi Hayashi, Kimio Yonesaka, Yasutaka Chiba, Takushi Yasuda, Kazuhiko Nakagawa

Esophagus : official journal of the Japan Esophageal Society　20　(2)　281-289　2022年12月9日

DOI： 10.1007/s10388-022-00976-9 　

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BACKGROUND: Neoadjuvant docetaxel plus cisplatin and 5-FU (NAC-DCF) and adjuvant nivolumab monotherapy are the standard care for locally advanced resectable esophageal squamous cell carcinoma (ESCC). However, no effective biomarkers have been found in perioperative setting. We investigated how programmed death-ligand 1 (PD-L1) changes before and after NAC-DCF and how it relates to the therapeutic effect of NAC-DCF in resectable ESCC. METHODS: PD-L1 expression in paired diagnostic biopsy and surgically resected tissues from ESCC patients who underwent surgical resection after receiving two or three NAC-DCF cycles was evaluated. PD-L1 positivity was defined as a combined positive score (CPS) of 10% ≤ . Gene expression analysis was conducted using samples before NAC-DCF. RESULTS: Sixty-six paired samples from 33 patients were included in PD-L1 expression analysis, and 33 Pre-NAC samples acquired by diagnostic biopsy were included in gene expression analysis. Pretreatment, 3 (9%), 13 (39%), and 17 (52%) patients harbored tumors with CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. After NAC-DCF, 5 (15%), 15 (45%), and 13 (39%) tumors presented CPS ranges of < 1%, 1%-10%, and 10% ≤ , respectively. The concordance rate between Pre-and Post-NAC-DCF samples was 45%. Patients with PD-L1-negative tumors both before and after NAC-DCF (n = 9) had shorter survival and different gene expression profile characterized by upregulation in WNT signaling or neutrophils. CONCLUSIONS: A substantial PD-L1 expression alteration was observed, resulting in low concordance rate before and after NAC-DCF. Tumors persistently lacking PD-L1 had distinct gene expression profile with worse clinical outcomes, raising the need for further investigation.
TRESBIEN (OGSG 2101): encorafenib, binimetinib and cetuximab for early recurrent stage II/III BRAF V600E-mutated colorectal cancer. 国際誌

Shogen Boku, Hironaga Satake, Takashi Ohta, Seiichiro Mitani, Kentaro Kawakami, Yozo Suzuki, Toshihiko Matsumoto, Tetsuji Terazawa, Eiki Yamazaki, Hiroko Hasegawa, Tatsuki Ikoma, Mamoru Uemura, Toshifumi Yamaguchi, Atsushi Naito, Yasunobu Ishizuka, Yukinori Kurokawa, Daisuke Sakai, Hisato Kawakami, Toshio Shimokawa, Toshimasa Tsujinaka, Takeshi Kato, Taroh Satoh, Yoshinori Kagawa

Future oncology (London, England)　18　(38)　4153-4160　2022年12月

DOI： 10.2217/fon-2022-0949 　

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The BRAF V600E mutation accounts for approximately 5% of colorectal cancer (CRC) cases and is an extremely poor prognostic factor. However, there are no clear recommendations regarding first-line therapy for patients with early recurrent BRAF V600E-mutated CRC, during or after adjuvant chemotherapy. Recently, a novel combination of encorafenib, binimetinib and cetuximab, showed a higher response rate than standard chemotherapy in patients with BRAF V600E-mutated CRC. Here we describe our plan for the TRESBIEN study (OGSG 2101), which is an open-label, multicenter, single-arm, phase II study designed to evaluate whether encorafenib, binimetinib and cetuximab are effective for patients with early recurrent BRAF V600E-mutated colorectal cancer, during or after adjuvant chemotherapy. The planned number of subjects is 25.
[The Current Status and Issues of Investigator-Initiated Clinical Trials in Japan].

Hisato Kawakami

Gan to kagaku ryoho. Cancer & chemotherapy　49　(12)　1295-1299　2022年12月

ISSN：0385-0684

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With the enforcement of the revised Pharmaceutical Affairs Law in 2003, physicians and dentists are now able to plan and conduct the"investigator-initiated"trial, whereas previously only companies were allowed to conduct such clinical trials. Although the number of investigator-initiated trials is increasing year by year, the high cost of conducting such trials and the difficulty of obtaining funds to cover the high cost are obstacles to their realization. In addition, the purpose of investigator- initiated clinical trials is to obtain approval for a drug or treatment, but in reality, there are many investigator -initiated clinical trials that do not aim for approval, and in some cases, the only difference between investigator-initiated clinical trials and specific clinical research is the approval status of the drug to be used in trials. In this article, the author will outline the current status and problems of investigator-initiated clinical trials in Japan in the midst of globalization of drug development, including the author's personal views.
First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50)

Ken Kato, Yuichiro Doki, Takashi Ogata, Satoru Motoyama, Hisato Kawakami, Masaki Ueno, Takashi Kojima, Yasuhiro Shirakawa, Morihito Okada, Ryu Ishihara, Yutaro Kubota, Carlos Amaya-Chanaga, Tian Chen, Yasuhiro Matsumura, Yuko Kitagawa

Esophagus　20　(2)　291-301　2022年11月19日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1007/s10388-022-00970-1 　

ISSN：1612-9059

eISSN：1612-9067

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Abstract Background Programmed cell death 1 (PD-1)-based treatments are approved for several cancers. CheckMate 648, a global, phase 3 trial, showed that first-line nivolumab (anti-PD-1 antibody) plus ipilimumab (NIVO + IPI) or nivolumab plus chemotherapy (NIVO + Chemo) significantly increased survival in advanced esophageal squamous cell carcinoma (ESCC) without new safety signals versus chemotherapy alone (Chemo). Methods We evaluated the Japanese subpopulation of CheckMate 648 (n = 394/970), randomized to receive first-line NIVO + IPI, NIVO + Chemo, or Chemo. Efficacy endpoints included overall survival (OS) and progression-free survival assessed by blinded independent central review in Japanese patients with tumor-cell programmed death-ligand 1 (PD-L1) expression ≥ 1% and in all randomized Japanese patients. Results In the Japanese population, 131, 126, and 137 patients were treated with NIVO + IPI, NIVO + Chemo, and Chemo, and 66, 62, and 65 patients had tumor-cell PD-L1 ≥ 1%, respectively. In patients with tumor-cell PD-L1 ≥ 1%, median OS was numerically longer with NIVO + IPI (20.2 months; hazard ratio [95% CI], 0.46 [0.30–0.71]) and NIVO + Chemo (17.3 months; 0.53 [0.35–0.82]) versus Chemo (9.0 months). In all randomized patients, median OS was numerically longer with NIVO + IPI (17.6 months; 0.68 [0.51–0.92]) and NIVO + Chemo (15.5 months; 0.73 [0.54–0.99]) versus Chemo (11.0 months). Grade 3–4 treatment-related adverse events were reported in 37%, 49%, and 36% of all patients in the NIVO + IPI, NIVO + Chemo, and Chemo arms, respectively. Conclusion Survival benefits with acceptable tolerability observed for NIVO + IPI and NIVO + Chemo treatments strongly support their use as a new standard first-line treatment in Japanese patients with advanced ESCC. ClinicalTrials.gov ID NCT03143153.
Histology Classification Highlights Differences in Efficacy of S-1 versus Capecitabine, in Combination with Cisplatin, for HER2-Negative Unresectable Advanced or Recurrent Gastric Cancer with Measurable Disease. 国際誌

Hisato Kawakami, Kazuhiro Nishikawa, Toshio Shimokawa, Kazumasa Fujitani, Shigeyuki Tamura, Shunji Endo, Michiya Kobayashi, Junji Kawada, Yukinori Kurokawa, Akira Tsuburaya, Takaki Yoshikawa, Junichi Sakamoto, Taroh Satoh, On Behalf Of The Herbis-Herbis-A And XParTS Ii Study Investigators

Cancers　14　(22)　2022年11月18日

DOI： 10.3390/cancers14225673 　

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It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40-60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology.
Oral formulation of bendamustine hydrochloride for patients with advanced solid tumors; a phase 1 study. 国際誌

Toshio Shimizu, Kazuhiko Nakagawa, Hidetoshi Hayashi, Tsutomu Iwasa, Hisato Kawakami, Satomi Watanabe, Noboru Yamamoto, Kan Yonemori, Takafumi Koyama, Jun Sato, Kenji Tamura, Keiichi Kikuchi, Kenichiro Akaike, Shiho Takeda, Masayuki Takeda

Investigational new drugs　41　(1)　1-12　2022年11月4日

DOI： 10.1007/s10637-022-01307-6 　

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To determine the maximum tolerated dose (MTD) and recommended dose (RD) of orally-administered bendamustine in Japanese patients with advanced solid tumors. The optimal dosing schedule, safety, pharmacokinetics, and preliminary antitumor effects were also evaluated. A multicenter, open-label trial with a standard 3 + 3 design and dose escalation by dose-limiting toxicity (DLT) was conducted. The treatment schedules were once daily for 7, 14, and 21 days every 3 weeks as one cycle. The total dose per cycle was increased from 175 to 840 mg/m2. Eighteen patients were enrolled in this study. DLT occurred in one of six patients at 75 mg/m2/day × 7 days, and one of three patients at 37.5 mg/m2/day × 14 days and 25 mg/m2/day × 21 days. However, the delayed recovery from a decrease in neutrophil or platelet count hampered the start of subsequent treatment cycles, and the trend was more prominent at 37.5 mg/m2/day × 14 days and 25 mg/m2/day × 21 days than in 75 mg/m2/day × 7 days. MTD was determined as 75 mg/m2/day × 7 days to allow acceptable hematologic recovery. The pharmacokinetics of orally-administered bendamustine were generally dose-dependent; however, the inter-individual variability is relatively large. The major adverse events were hematologic toxicities; gastrointestinal disorders were generally mild. Adverse drug reactions did not lead to the discontinuation of the drug. A partial response was observed in two of six patients (prostatic small cell carcinoma and thymic carcinoma) at 75 mg/m2/day × 7 days. The RD and optimal dosing schedule of orally-administered bendamustine was 75 mg/m2 once daily for 7 days every 3 weeks for the treatment of advanced solid tumors. (Trial registration number ClinicalTrials.gov NCT03604679. Registration date July 27, 2018).
Mechanisms of primary and acquired resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer: A multiplex immunohistochemistry-based single-cell analysis. 国際誌

Kohsuke Isomoto, Koji Haratani, Takahiro Tsujikawa, Yusuke Makutani, Hisato Kawakami, Masayuki Takeda, Kimio Yonesaka, Kaoru Tanaka, Tsutomu Iwasa, Hidetoshi Hayashi, Akihiko Ito, Kazuto Nishio, Kazuhiko Nakagawa

Lung cancer (Amsterdam, Netherlands)　174　71-82　2022年10月30日

DOI： 10.1016/j.lungcan.2022.10.012 　

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OBJECTIVE: Immune checkpoint inhibitors (ICIs) have become a key therapeutic modality for advanced non-small cell lung cancer (NSCLC), but most patients experience primary or acquired resistance to these drugs. We here explored the mechanisms underlying both types of ICI resistance by analysis of the tumor immune microenvironment (TME). MATERIALS AND METHODS: Four patients who experienced a long-term response to ICI treatment (progression-free survival [PFS] of ≥12 months) followed by disease progression, after which a rebiopsy was immediately performed (cohort-A), as well as four patients who experienced early tumor progression during ICI treatment (PFS of <9 weeks, cohort-B) were enrolled in this retrospective study. The pretreatment TME was evaluated by 16- or 17-color multiplex immunohistochemistry (mIHC)-based spatial profiling at the single-cell level for both cohorts. In cohort-A, changes in the TME after disease progression during ICI treatment were also investigated by mIHC analysis and transcriptomic analysis. RESULTS: Pretreatment tumor tissue from cohort-B manifested poor infiltration of tumor-reactive CD8+ T cells characterized by CD39 and CD103 expression or by programmed cell death-1 expression, implicating insufficient recognition of tumor cells by CD8+ T cells as a mechanism of primary ICI resistance. Analysis of the paired tumor specimens from cohort-A revealed various changes in the TME associated with acquired ICI resistance, including substantial infiltration of myeloid-derived suppressor cells and M2-type tumor-associated macrophages without a marked decline in the number of tumor-reactive CD8+ T cells; a decrease in the number of tumor-reactive CD8+ T cells; and an apparent decrease in neoantigen presentation by tumor cells. CONCLUSION: The presence of intratumoral tumor-reactive CD8+ T cells may be a prerequisite for a long-term response to ICI treatment in advanced NSCLC, but it is not sufficient for cancer cell eradication. Various TME profiles are associated with acquired ICI resistance, suggesting that patient-specific strategies to overcome such resistance may be necessary.
A phase II study of S-1 therapy for patients with advanced and recurrent esophageal cancer resistant or intolerable to fluorouracil, platinum, and taxane therapy (OGSG 1404).

Motoo Nomura, Takayuki Kii, Junji Kawada, Masashi Hirota, Takashi Ohta, Jin Matsuyama, Daisuke Sakai, Toshio Shimokawa, Yukinori Kurokawa, Hisato Kawakami, Toshimasa Tsujinaka, Taroh Satoh

Esophagus : official journal of the Japan Esophageal Society　19　(4)　711-716　2022年10月

DOI： 10.1007/s10388-022-00931-8 　

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BACKGROUND: Fluorouracil (FU), platinum (PT), and taxane (TAX) therapy was the standard chemotherapy for esophageal squamous cell carcinoma (ESCC) before the era of anti-programmed death-1 antibodies. The aim of this phase II trial was to evaluate the efficacy and safety of S-1 monotherapy for patients with recurrent or metastatic (R/M) ESCC resistant or intolerable to FU, PT, and TAX therapy. METHODS: Eligible patients had R/M ESCC; no prior S-1 use; were intolerant or refractory to prior FU, PT, and TAX therapy; aged ≧ 20 years; and Eastern Cooperative Oncology Group performance status 0 or 1. S-1 was administered orally from days 1 to 28, every 6 weeks until disease progression. The primary endpoint was the disease control rate (DCR) for each patient, assessed by Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints were overall survival, progression-free survival, time to treatment failure, response rate, and toxicity. RESULTS: Between October 2015 and December 2017, 17 patients were recruited, and the trial was terminated because of slow accrual. The DCR was 46.7%. The response rate was 13.3%. The median progression-free survival was 2.0 months. The median time to treatment failure was 1.9 months. The median overall survival was 8.4 months, and the 1 year overall survival rate was 30.5%. CONCLUSIONS: Although this trial closed early because of slow accrual, we observed modest clinical activity with S-1 in patients with R/M ESCC who could not tolerate or whose tumors were refractory to FU, PT, and TAX therapy.
食道癌・接合部癌における免疫チェックポイント阻害剤の意義と課題食道扁平上皮癌における術前DCF療法によるPD-L1発現の変化とその臨床的意義

三谷誠一郎, 川上尚人, 黒崎隆, 稲垣千晶, 林秀敏, 米阪仁雄, 白石治, 安田卓司, 中川和彦

日本食道学会学術集会プログラム・抄録集　76回　7-7　2022年9月
出版者・発行元： (NPO)日本食道学会
Phase IIb study of pembrolizumab combined with S-1 + oxaliplatin or S-1 + cisplatin as first-line chemotherapy for gastric cancer. 国際誌

Kensei Yamaguchi, Keiko Minashi, Daisuke Sakai, Tomohiro Nishina, Yasushi Omuro, Masahiro Tsuda, Shiroh Iwagami, Hisato Kawakami, Taito Esaki, Naotoshi Sugimoto, Takashi Oshima, Ken Kato, Kenji Amagai, Hisashi Hosaka, Keigo Komine, Hisateru Yasui, Yuji Negoro, Kenji Ishido, Takahiro Tsushima, Shirong Han, Shinichi Shiratori, Tomoko Takami, Kohei Shitara

Cancer science　113　(8)　2814-2827　2022年8月

DOI： 10.1111/cas.15462 　

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The KEYNOTE-659 study evaluated the efficacy and safety of first-line pembrolizumab plus S-1 and oxaliplatin (SOX) (cohort 1) or S-1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open-label phase IIb study enrolled patients with advanced programmed death-ligand 1 (PD-L1)-positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)-negative G/GEJ adenocarcinoma. The primary end-point was the objective response rate (ORR). Other end-points were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow-up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment-related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD-L1-positive, HER2-negative G/GEJ adenocarcinoma.
Neoadjuvant docetaxel, oxaliplatin and S-1 therapy for the patients with large type 3 or type 4 gastric cancer (OGSG1902): protocol of a multi-center, phase II study. 国際誌

Shunji Endo, Tetsuji Terazawa, Masahiro Goto, Ryo Tanaka, Takeshi Kato, Kazumasa Fujitani, Hisato Kawakami, Daisuke Sakai, Yukinori Kurokawa, Toshimasa Tsujinaka, Toshio Shimokawa, Taroh Satoh

BMC cancer　22　(1)　811-811　2022年7月23日

DOI： 10.1186/s12885-022-09890-w 　

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BACKGROUND: Large type 3 and type 4 gastric cancers have extremely poor prognoses. To address this, neoadjuvant chemotherapy may be a promising approach. The phase III JCOG0501 study, conducted to confirm the superiority of neoadjuvant S-1 plus cisplatin followed by D2 gastrectomy over upfront surgery, showed no survival benefit for neoadjuvant S-1 plus cisplatin. In Korea, the PRODIGY study, which was a phase III study of neoadjuvant docetaxel plus oxaliplatin plus S-1 (DOS) followed by surgery and adjuvant S-1 versus surgery and adjuvant S-1 for gastric cancer of T2-3N+ or T4Nany, showed that progression-free survival (PFS) was significantly superior in the neoadjuvant DOS arm. Therefore, DOS therapy may be a promising candidate for preoperative chemotherapy for large type 3 or type 4 gastric cancer. METHODS: Preoperative docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 will be intravenously administered on day1 every three weeks. S-1 will be orally administered 80 mg/m2 on days 1-14 of a 21-day cycle. Patients will receive three courses of treatment and gastrectomy with ≥D2 lymph node dissection. Postoperative S-1 plus docetaxel therapy (DS) will be administered according to the JACCRO GC-07 (START-2) study. The primary endpoint is the 3-year PFS rate. Secondary endpoints include PFS time, overall survival time, pathological response rate, response rate according to RECIST version1.1, proportion of completion of neoadjuvant chemotherapy, R0 resection rate, proportion of completion of surgery, proportion of completion of protocol treatment, proportion of negative conversion of CY, adverse event occurrence rate, and nutritional evaluation. The null hypothesis for the 3-year PFS rate is 45% and the expected value is 60%. The total sample size is 46 considering that the registration period and follow-up period are two and three years, respectively. DISCUSSION: This is a prospective, multicenter, single-arm, open-label, phase II trial assessing the efficacy and safety of preoperative DOS and postoperative DS for large type 3 or type 4 gastric cancer. The results will inform future phase III trials and are expected to lead to new treatment strategies for large type 3 or type 4 gastric cancer. TRIAL REGISTRATION: Registered with Japan Registry of Clinical Trials on October 11, 2019 ( jRCTs051190060 ).
Protocol of OGSG 1901: a phase II trial of ramucirumab plus irinotecan for patients with early relapsed gastric cancer during or after adjuvant docetaxel plus S - 1 therapy. 国際誌

Toshifumi Yamaguchi, Hisato Kawakami, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Masahiro Goto, Taroh Satoh

BMC cancer　22　(1)　773-773　2022年7月15日

DOI： 10.1186/s12885-022-09844-2 　

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BACKGROUND: Although docetaxel plus S-1 adjuvant chemotherapy after gastrectomy with D2 lymphadenectomy has been a standard of treatment for stage III gastric cancer, there is no established chemotherapy for patients with recurrence during or within six months after the completion of adjuvant docetaxel plus S-1 therapy. METHODS: The OGSG 1901 trial is a prospective, open-label, multicenter, phase II trial evaluating ramucirumab plus irinotecan for gastric cancer patients with early relapse after adjuvant docetaxel plus S-1 therapy. The key eligibility criteria were: 1) histologically confirmed gastric adenocarcinoma 2) patients who were on docetaxel plus S-1 adjuvant chemotherapy after the confirmation of pathological stage III, 3) patients with early relapse, i.e., recurrence during or within 6 months after the completion of docetaxel plus S-1 therapy, and 4) patient with Eastern Cooperative Oncology Group performance status of 0-1. Irinotecan (150 mg/m2, day 1) and ramucirumab (8 mg/kg, day 1) will be administered every 2 weeks. The primary endpoint is overall survival, and the secondary endpoints are overall response rate, progression-free survival, and safety. The number of patients has been set at 40 based on the threshold and expected median survival times of 7 and 11 months, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods are 2 and 1.5 years, respectively. DISCUSSION: The results of this trial will indicate whether the ramucirumab with irinotecan regimen has the potential to be a recommended treatment regimen for patients with recurrence gastric cancer during or within 6 months after the completion of adjuvant docetaxel plus S-1 therapy. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials ( jRCTs05119071 , October 6, 2019).
BRCA2シングルサイト検査を同時に受検した姉妹の遺伝カウンセリング

大道納菜子, 川上尚人, 池川敦子, 小田いつき, 奥田亜弥, 木下善仁, 田村和朗, 西郷和真

日本遺伝カウンセリング学会誌　43　(2)　138-138　2022年6月
出版者・発行元： (一社)日本遺伝カウンセリング学会
ISSN：1347-9628
Three-Year Outcomes of a Phase II Study of Perioperative Capecitabine Plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601). 国際誌

Jin Matsuyama, Tetsuji Terazawa, Masahiro Goto, Ryohei Kawabata, Shunji Endo, Motohiro Imano, Shoichiro Fujita, Yusuke Akamaru, Hirokazu Taniguchi, Mitsutoshi Tatsumi, Sang-Woong Lee, Hisato Kawakami, Yukinori Kurokawa, Toshio Shimokawa, Daisuke Sakai, Takeshi Kato, Kazumasa Fujitani, Taroh Satoh

The oncologist　27　(4)　251-e304　2022年4月5日

DOI： 10.1093/oncolo/oyab061 　

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BACKGROUND: We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. METHODS: The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). RESULTS: Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. CONCLUSION: Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).
食道癌2次化学療法におけるDTXとPTXのランダム化比較第II相試験(OGSG1201)

川田純司, 山本幸子, 紀貴之, 原浩紀, 川端良平, 竹野淳, 松山仁, 上田修吾, 川上尚人, 大北仁裕, 遠藤俊治, 木村豊, 柳原一広, 奥野達哉, 黒川幸典, 下川敏雄, 佐藤太郎

日本外科学会定期学術集会抄録集　122回　SF-5　2022年4月
出版者・発行元： (一社)日本外科学会
食道癌2次化学療法におけるDTXとPTXのランダム化比較第II相試験(OGSG1201)

川田純司, 山本幸子, 紀貴之, 原浩紀, 川端良平, 竹野淳, 松山仁, 上田修吾, 川上尚人, 大北仁裕, 遠藤俊治, 木村豊, 柳原一広, 奥野達哉, 黒川幸典, 下川敏雄, 佐藤太郎

日本外科学会定期学術集会抄録集　122回　SF-5　2022年4月
出版者・発行元： (一社)日本外科学会
Sequential Treatment Strategy Using Fluoropyrimidine plus Bevacizumab Followed by Oxaliplatin for Metastatic Colorectal Cancer: A Phase II Study (OGSG 1107). 国際誌

Toshifumi Yamaguchi, Motoki Yoshida, Hisato Kawakami, Takayuki Kii, Hiroko Hasegawa, Takahiro Miyamoto, Tetsuji Terazawa, Fukutaro Shimamoto, Masayoshi Yasui, Daisuke Sakai, Toshio Shimokawa, Yukinori Kurokawa, Masahiro Goto, Taroh Satoh

Gastrointestinal tumors　9　(1)　27-36　2022年3月

DOI： 10.1159/000522610 　

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Introduction: Previous prospective studies suggest that the sequential use of cytotoxic agents, such as oxaliplatin, in patients with metastatic colorectal cancer (mCRC) has the potential to improve prognosis and maintain quality of life than combination chemotherapy. The purpose of this study was to investigate the feasibility and effectiveness of a sequential treatment strategy consisting of an initial therapy (capecitabine, S-1, or 5-fluorouracil with leucovorin [LV/5-FU] plus bevacizumab) and subsequent therapy (i.e., initial therapy plus oxaliplatin) for mCRC. Methods: The primary endpoint was second progression-free survival (2nd PFS) between the start of initial therapy and tumor progression after sequential therapy; secondary endpoints were PFS after initial treatment, overall survival (OS), objective response rate (ORR), and safety. Results: Sixty-six patients were planned to be recruited. However, owing to a slow accrual rate, recruitment was terminated when only 19 patients were enrolled between 2011 and 2015; 4, 10, and 5 patients were administered capecitabine plus bevacizumab, S-1 plus bevacizumab, and LV/5-FU plus bevacizumab, respectively. The proportions of those with a KRAS status (wild-type/mutant/unknown) were 26%, 21%, and 53%, respectively. The median 2nd PFS and OS were 19.1 months and not reached, respectively. The ORR was 45.5% in the initial therapy and 16.7% in the subsequent therapy. Grade 3/4 toxicities included neutropenia (5%), proteinuria (5%), and hypertension (47%). Conclusion: Although our data are limited and preliminary, the sequential treatment strategy may provide a survival benefit in patients with mCRC. Further investigation of this treatment approach is warranted.
HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non-Small Cell Lung Cancer. 国際誌

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Koji Haratani, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Yasutaka Chiba, Asuka Tsuya, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Maki Kobayashi, Ryoto Yoshimoto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

Clinical cancer research : an official journal of the American Association for Cancer Research　28　(2)　390-403　2022年1月15日

DOI： 10.1158/1078-0432.CCR-21-3359 　

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PURPOSE: EGFR-tyrosine kinase inhibitor (TKI) is a standard first-line therapy for activated EGFR-mutated non-small cell lung cancer (NSCLC). Treatment options for patients with acquired EGFR-TKI resistance are limited. HER3 mediates EGFR-TKI resistance. Clinical trials of the HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated its anticancer activity in EGFR-mutated NSCLC; however, the mechanisms that regulate HER3 expression are unknown. This study was conducted with the aim to clarify the mechanisms underlying HER3 regulation in EGFR-mutated NSCLC tumors and explored the strategy for enhancing the anticancer activity of HER3-DXd in EGFR-mutated NSCLC. EXPERIMENTAL DESIGN: Paired tumor samples were obtained from 48 patients with EGFR-mutated NSCLC treated with EGFR-TKI(s). HER3 expression was immunohistochemically quantified with H-score, and genomic alteration and transcriptomic signature were tested in tumors from pretreatment to post-EGFR-TKI resistance acquisition. The anticancer efficacy of HER3-DXd and osimertinib was evaluated in EGFR-mutated NSCLC cells. RESULTS: We showed augmented HER3 expression in EGFR-mutated tumors with acquired EGFR-TKI resistance compared with paired pretreatment samples. RNA sequencing revealed that repressed PI3K/AKT/mTOR signaling was associated with HER3 augmentation, especially in tumors from patients who received continuous EGFR-TKI therapy. An in vitro study also showed that EGFR-TKI increased HER3 expression, repressed AKT phosphorylation in multiple EGFR-mutated cancers, and enhanced the anticancer activity of HER3-DXd. CONCLUSIONS: Our findings help clarify the mechanisms of HER3 regulation in EGFR-mutated NSCLC tumors and highlight a rationale for combination therapy with HER3-DXd and EGFR-TKI in EGFR-mutated NSCLC.
Correction: KRAS Inhibitor Resistance in MET-Amplified KRAS G12C Non-Small Cell Lung Cancer Induced By RAS- and Non-RAS-Mediated Cell Signaling Mechanisms. 国際誌

Shinichiro Suzuki, Kimio Yonesaka, Takeshi Teramura, Toshiyuki Takehara, Ryoji Kato, Hitomi Sakai, Koji Haratani, Junko Tanizaki, Hisato Kawakami, Hidetoshi Hayashi, Kazuko Sakai, Kazuto Nishio, Kazuhiko Nakagawa

Clinical cancer research : an official journal of the American Association for Cancer Research　28　(2)　428-428　2022年1月15日

DOI： 10.1158/1078-0432.CCR-21-4240 　
NOTCH gene alterations in metastatic colorectal cancer in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN)

Kajiwara, T., Nishina, T., Nakasya, A., Yamashita, N., Yamashita, R., Nakamura, Y., Shiozawa, M., Yuki, S., Taniguchi, H., Hara, H., Ohta, T., Esaki, T., Shinozaki, E., Takashima, A., Moriwaki, T., Denda, T., Ohtsubo, K., Sunakawa, Y., Horita, Y., Kawakami, H., Kato, T., Satoh, T., Ando, K., Mizutani, T., Yasui, H., Goto, M., Okuyama, H., Yamazaki, K., Yoshino, T., Hyodo, I.

Journal of Cancer Research and Clinical Oncology　148　(10)　2022年

DOI： 10.1007/s00432-022-04064-4 　

ISSN：1432-1335 0171-5216
Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer. 国際誌

Yusuke Makutani, Hisato Kawakami, Takahiro Tsujikawa, Kanako Yoshimura, Yasutaka Chiba, Akihiko Ito, Junichiro Kawamura, Koji Haratani, Kazuhiko Nakagawa

Frontiers in oncology　12　956270-956270　2022年

DOI： 10.3389/fonc.2022.956270 　

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Matrix metalloproteinase 14 (MMP14) expression is implicated in progression of colorectal cancer, but its role in the tumor microenvironment (TME) has been unclear. The relevance of MMP14 to colorectal cancer progression was explored by analysis of transcriptomic data for colorectal adenocarcinoma patients (n = 592) in The Cancer Genome Atlas. The role of MMP14 in the TME was investigated in a retrospective analysis of tumor samples from 86 individuals with stage III colorectal cancer by single cell-based spatial profiling of MMP14 expression as performed by 12-color multiplex immunohistochemistry (mIHC). Analysis of gene expression data revealed that high MMP14 expression was associated with tumor progression and implicated both cancer-associated fibroblasts (CAFs) and tumor-associated macrophages in such progression. Spatial profiling by mIHC revealed that a higher percentage of MMP14+ cells among intratumoral CAFs (MMP14+ CAF/CAF ratio) was associated with poorer relapse-free survival. Multivariable analysis including key clinical factors identified the MMP14+ CAF/CAF ratio as an independent poor prognostic factor. Moreover, the patient subset with both a high MMP14+ CAF/CAF ratio and a low tumor-infiltrating lymphocyte density showed the worst prognosis. Our results suggest that MMP14+ CAFs play an important role in progression of stage III colorectal cancer and may therefore be a promising therapeutic target.
Second-line pembrolizumab versus chemotherapy in Japanese patients with advanced esophageal cancer: subgroup analysis from KEYNOTE-181.

Kei Muro, Takashi Kojima, Toshikazu Moriwaki, Ken Kato, Fumio Nagashima, Hisato Kawakami, Ryu Ishihara, Takashi Ogata, Taroh Satoh, Keiichi Iwakami, Shirong Han, Naoyoshi Yatsuzuka, Tomoko Takami, Pooja Bhagia, Toshihiko Doi

Esophagus : official journal of the Japan Esophageal Society　19　(1)　137-145　2022年1月

DOI： 10.1007/s10388-021-00877-3 　

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BACKGROUND: Safe and effective treatments for advanced esophageal cancer are an unmet need in Japan. We report results of a subgroup analysis of Japanese patients enrolled in KEYNOTE-181, a randomized, open-label, phase 3 study of pembrolizumab versus chemotherapy as second-line therapy for patients with advanced or metastatic esophageal cancer whose disease progressed after standard first-line therapy. METHODS: Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg every 3 weeks or investigator's choice of paclitaxel, docetaxel, or irinotecan. Efficacy was evaluated in all Japanese patients and in those with programmed death ligand 1 combined positive score ≥ 10. RESULTS: Of the 152 Japanese patients enrolled (pembrolizumab, n = 77; chemotherapy, n = 75), 150 (98.7%) had squamous cell carcinoma and 79 (52.0%) had combined positive score ≥ 10. At the final analysis, median overall survival was improved among all patients (12.4 vs 8.2 months with pembrolizumab and chemotherapy, respectively; hazard ratio, 0.68; 95% CI 0.48-0.97) and patients with combined positive score ≥ 10 (12.6 vs 8.4 months; hazard ratio, 0.68; 95% CI 0.42-1.10). Fewer patients had any-grade (74.0% vs 95.9%) or grade 3-5 (16.9 vs 50.0%) treatment-related adverse events with pembrolizumab than with chemotherapy. CONCLUSION: Consistent with the global trial results, second-line pembrolizumab therapy showed a survival benefit and a favorable safety profile compared with chemotherapy in Japanese patients with advanced esophageal cancer.
原発不明癌に対するNivolumab(ONO-4538)の有効性を検討する第II相試験

谷崎潤子, 鈴木慎一郎, 金村宙昌, 岩朝勤, 川上尚人, 田中薫, 吉田健史, 米阪仁雄, 伊藤彰彦, 坂井和子, 木寺康裕, 福岡和也, 千葉康敬, 西尾和人, 中川和彦, 林秀敏

近畿大学医学雑誌　46　(3-4)　20A-20A　2021年12月
出版者・発行元：近畿大学医学会
ISSN：0385-8367
EGFR-TKIはHER3の発現を促し、HER3阻害剤パトリツマブデルクステカンの有効性を高める(EGFR-TKI augments HER3 expression and enhances the efficacy of HER3 targeting patritumab deruxtecan)

米阪仁雄, 谷崎潤子, 前西修, 川上尚人, 田中薫, 林秀敏, 坂井和子, 後藤大輝, 小林真季, 吉本龍人, 大塚絵里, 沖田弘明, 舟橋賢記, 橋本悠里, 廣谷賢志, 明松隆志, 西尾和人, 中川和彦

肺癌　61　(6)　623-623　2021年10月
出版者・発行元： (NPO)日本肺癌学会
ISSN：0386-9628

eISSN：1348-9992
MET-amplifiedによるKRASG12C阻害薬の獲得耐性とメカニズム

鈴木慎一郎, 米阪仁雄, 寺村岳士, 竹原俊幸, 加藤了資, 酒井瞳, 原谷浩司, 谷崎潤子, 川上尚人, 林秀敏, 坂井和子, 西尾和人, 中川和彦

肺癌　61　(6)　629-629　2021年10月
出版者・発行元： (NPO)日本肺癌学会
ISSN：0386-9628

eISSN：1348-9992
ベンダムスチン塩酸塩経口剤(SyB C-0501)の進行性固形がん患者に対する第1相臨床試験

武田真幸, 中川和彦, 林秀敏, 岩朝勤, 川上尚人, 渡邉諭美, 山本昇, 米盛勧, 小山隆文, 佐藤潤, 田村研治, 菊池圭一, 赤池健一郎, 竹田志保, 清水俊雄

日本癌治療学会学術集会抄録集　59回　O13-5　2021年10月
出版者・発行元： (一社)日本癌治療学会
切除不能進行・再発大腸癌に対する後方ラインにおけるレゴラフェニブ療法とS-1+ベバシズマブ併用療法の無作為化比較第II相試験(OGSG1301)

児玉紘幸, 吉田元樹, 後藤昌弘, 中村将人, 長谷川裕子, 池田温至, 徳永行彦, 谷川和史, 寺澤哲志, 坂井大介, 黒川幸典, 川上尚人, 下川敏雄, 佐藤太郎

癌と化学療法　48　(10)　1241-1246　2021年10月
出版者・発行元： (株)癌と化学療法社
ISSN：0385-0684
[Regorafenib versus S-1 plus Bevacizumab for Metastatic Colorectal Cancer as Salvage Line-A Phase Ⅱ Study (OGSG1301)].

Hiroyuki Kodama, Motoki Yoshida, Masahiro Goto, Masato Nakamura, Hiroko Hasegawa, Atsushi IKeda, Yukihiko Tokunaga, Kazufumi Tanigawa, Tetsuji Terazawa, Daisuke Sakai, Yukinori Kurokawa, Hisato Kawakami, Toshio Shimokawa, Taroh Satoh

Gan to kagaku ryoho. Cancer & chemotherapy　48　(10)　1241-1246　2021年10月

ISSN：0385-0684

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BACKGROUND: Regorafenib(Rego)is the salvage line standard treatment for metastatic colorectal cancer(mCRC), which often causes severe toxicities, such as hand-foot syndrome. Previously, we reported that in phase Ⅱ study, S-1 plus bevacizumab( Bev)(SB)showed favorable anticancer activity and feasibility as a salvage line. The aim of this study was to evaluate 2 treatments for mCRC as salvage line. PATIENTS AND METHODS: In this multicenter phase Ⅱ study, the patients were randomly assigned(1:1)to the Rego or SB group. In the Rego group, Rego 160 mg/kg body weight was orally administered every 28 days for 21 days. In the SB group, S-1 was orally administered every 42 days for 28 days, according to body surface area, and Bev 5 mg/kg was administered by intravenous infusion on days 1, 15, and 29. Administration of S-1 every 21 days for 14 days and Bev 7.5 mg/kg on day 1 was also permitted. The primary endpoint was overall survival(OS), and the planned sample size was 86. RESULTS: This study was ended prematurely due to poor accrual. Overall, 8 patients were enrolled from 6 institutions between Oct 2013 and May 2015. Although 4 patients were assigned to each group, one patient in the Rego group was excluded after enrollment. The median OS in the Rego and SB groups was 30.2 months and 6.6 months, respectively(hazard ratio: 0.205, p=0.123). The median progression-free survival in the Rego and SB groups was 3.7 months and 1.6 months, respectively. The disease control rate in the Rego and SB groups was 100% and 75%, respectively. The Grade 3 or 4 adverse events were increased, including AST/ALT(n=1, 25%), hyponatremia(n=1, 25%), hand-foot syndrome(n=1, 25%), hypertension(n=1, 25%), and proteinuria(n=1, 25%)in the Rego group and colitis( n=1, 25%)in the SB group; the treatment was discontinued. CONCLUSION: Despite the fact that data could only be collected from a small number of patients, SB is not recommended as salvage line for mCRC.
Randomized phase II study of CPT-11 versus PTX versus each combination chemotherapy with S-1 for advanced gastric cancer that is refractory to S-1 or S-1 plus CDDP: OGSG0701.

Tomono Kawase, Hiroshi Imamura, Masahiro Goto, Yutaka Kimura, Shugo Ueda, Jin Matsuyama, Kazuhiro Nishikawa, Naotoshi Sugimoto, Junya Fujita, Takao Tamura, Norimasa Fukushima, Hisato Kawakami, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

International journal of clinical oncology　26　(10)　1871-1880　2021年8月28日

DOI： 10.1007/s10147-021-01984-y 　

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BACKGROUND: To compare irinotecan-alone, paclitaxel-alone, and each combination chemotherapy with S-1 in patients with advanced gastric cancer (AGC) that is refractory to S-1 or S-1 plus cisplatin (SP). METHODS: Patients with AGC after first-line chemotherapy with S-1 or SP, or patients during adjuvant chemotherapy or within 26 weeks after adjuvant chemotherapy completion with S-1 with confirmed disease progression were eligible. Patients were randomly divided into four groups based on treatment: irinotecan-alone (irinotecan; 150 mg/m2, day 1, q14 days), paclitaxel-alone (paclitaxel; 80 mg/m2, days 1, 8, 15, q28 days), S-1 plus irinotecan (irinotecan; 80 mg/m2, days 1, 15, S-1; 80 mg/m2, days 1-21, q35 days), and S-1 plus paclitaxel (paclitaxel; 50 mg/m2, day1, 8, S-1; 80 mg/m2, days 1-14, q21 days). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), response rate, and safety. RESULTS: From July 2008 to March 2012, 127 patients were enrolled. No difference in median OS was observed in the irinotecan vs. paclitaxel groups or in the monotherapy groups vs. the S-1 combination therapy groups. Median PFS was longer in the paclitaxel group compared with the irinotecan group (4.1 vs. 3.6 months, p = 0.035), although no difference was observed when comparing monotherapy vs. S-1 combination. The most common grade 3 to 4 hematological adverse events were neutropenia with no difference in incidence rate across the treatment groups. CONCLUSIONS: There was no difference in OS between irinotecan and paclitaxel no in OS prolongation of S-1 combination therapy in second-line chemotherapy.
Real-world effectiveness of nivolumab in advanced gastric cancer: the DELIVER trial (JACCRO GC-08).

Yoshikazu Takahashi, Yu Sunakawa, Eisuke Inoue, Ryohei Kawabata, Atsushi Ishiguro, Yosuke Kito, Yusuke Akamaru, Masazumi Takahashi, Hiroshi Yabusaki, Jin Matsuyama, Akitaka Makiyama, Masahiro Tsuda, Takahisa Suzuki, Hisateru Yasui, Ryo Matoba, Hisato Kawakami, Takako Eguchi Nakajima, Kei Muro, Wataru Ichikawa, Masashi Fujii

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　25　(1)　235-244　2021年8月24日

DOI： 10.1007/s10120-021-01237-x 　

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BACKGROUND: There is no large real-world data regarding efficacy and safety of immunotherapy in gastric cancer (GC). Although some tumors can grow rapidly after immunotherapy, the patient proportions and survival outcomes are unclear in GC. METHODS: A multicenter, prospective observational study was performed to evaluate clinical outcomes including survival time, safety, and tumor behavior of nivolumab treatment for patients with advanced GC. Primary endpoint was overall survival (OS), and secondary endpoints included response rate (RR), disease control rate (DCR), progression-free survival (PFS), tumor growth rate (TGR) at first evaluation, and safety. RESULTS: Of 501 enrolled patients, 487 were evaluable (median age 70 years, 71% male, performance status 0/1/2 [42%/44%/14%], 21% HER2-pos, 42% patients with ascites). Median OS was 5.82 months (95% CI 5.29-7.00) with a 1-year survival rate of 30% and median PFS of 1.84 months (95% CI 1.71-1.97). The DCR was 39.4% and the RR was 14.2% (95% CI 10.3-18.8) in 282 patients with measurable lesions. In 219 patients evaluable for TGR, 20.5% were identified as hyperprogressive disease (HPD). OS from the first evaluation of patients with HPD was shorter compared with non-HPD (HR 1.77, 95% CI 1.25-2.51, P = 0.001), but it was not worse than that of patients with progression and non-HPD (HR 1.05, 95% CI 0.72-1.53, P = 0.8). A multivariate analysis revealed the presence of peritoneal metastasis was a prognostic factor for OS and PFS. CONCLUSIONS: Our real-world data demonstrated the comparable survival time to a previous clinical trial and revealed the frequency and prognosis of patients with HPD in advanced GC treated with nivolumab.
KRAS inhibitor-resistance in MET-amplified KRAS G12C non-small cell lung cancer induced by RAS- and non-RAS-mediated cell signaling mechanisms. 国際誌

Shinichiro Suzuki, Kimio Yonesaka, Takeshi Teramura, Toshiyuki Takehara, Ryoji Kato, Hitomi Sakai, Koji Haratani, Junko Tanizaki, Hisato Kawakami, Hidetoshi Hayashi, Kazuko Sakai, Kazuto Nishio, Kazuhiko Nakagawa

Clinical cancer research : an official journal of the American Association for Cancer Research　27　(20)　5697-5707　2021年8月7日

DOI： 10.1158/1078-0432.CCR-21-0856 　

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PURPOSE: Treatment with KRAS G12C inhibitors such as sotorasib can produce substantial regression of tumors in some patients with non-small cell lung cancer (NSCLC). These patients require alternative treatment after acquiring resistance to the inhibitor. The mechanisms underlying this acquired resistance are unclear. The purpose of this study was to identify the mechanisms underlying acquired sotorasib resistance, and to explore potential treatments for rescuing patients with sotorasib-resistant KRAS G12C NSCLC cells. EXPERIMENTAL DESIGN: Clones of sotorasib-sensitive KRAS G12C NSCLC H23 cells exposed to different concentrations of sotorasib were examined using whole-genomic transcriptome analysis, multiple receptor kinase phosphorylation analysis, and gene copy number evaluation. The underlying mechanisms of resistance were investigated using immunological examination, and a treatment aimed at overcoming resistance was tested in vitro and in vivo Results: Unbiased screening detected subclonal evolution of MET amplification in KRAS G12C NSCLC cells that had developed resistance to sotorasib in vitro MET knockdown using siRNA restored susceptibility to sotorasib in these resistant cells. MET activation by its amplification reinforced RAS cycling from its inactive form to its active form. In addition to RAS-mediated MEK-ERK induction, MET induced AKT activation independently of RAS. Crizotinib, a MET inhibitor, restored sensitivity to sotorasib by eliminating RAS-MEK-ERK as well as AKT signaling. MET/KRAS G12C dual inhibition led to tumor shrinkage in sotorasib-resistant xenograft mice. CONCLUSIONS: MET amplification leads to the development of resistance to KRAS G12C inhibitors in NSCLC. Dual blockade of MET and KRAS G12C could be a treatment option for MET amplified, KRAS G12C-mutated NSCLC.
Integrative analysis of gut microbiome and host transcriptomes reveals associations between treatment outcomes and immunotherapy-induced colitis. 国際誌

Toshiharu Sakurai, Marco A De Velasco, Kazuko Sakai, Tomoyuki Nagai, Hiroki Nishiyama, Kentaro Hashimoto, Hirotsugu Uemura, Hisato Kawakami, Kazuhiko Nakagawa, Hiroyuki Ogata, Kazuto Nishio, Masatoshi Kudo

Molecular oncology　2021年7月16日
出版者・発行元： Wiley
DOI： 10.1002/1878-0261.13062 　

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Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies. Although the gut microbiome is known to influence the efficacy of ICIs on epithelial tumors, the functional interactions between gut taxa and colonic mucosa remain poorly understood. Here we performed transcriptomic profiling and 16S rRNA sequencing to investigate the relationships between mucosal gene expression and microbial composition with ICI responses and gastrointestinal immune-related adverse events (GI irAEs). In responders, genes related to DNA repair and cell cycle signatures were enriched in responders whereas signatures related to innate immune response, NFAT and IFN-γ signaling pathways were enriched in nonresponders. Gut microbial composition revealed an association between moderate GI irAE and favorable response to ICI therapy. Favorable therapeutic responses to ICI and GI irAE treatments were associated with taxa classified as Enterobacteriaceae and were related to ribonucleoprotein complex biogenesis, cytokine-mediated signaling pathway, tRNA metabolic process, and ribonucleoprotein complex assembly in the colon. These findings open new perspectives for improving the efficacy and safety of cancer immunotherapy.
Serum lactate dehydrogenase is a predictive biomarker in patients with oropharyngeal cancer undergoing radiotherapy: A retrospective study on predictive factors. 国際誌

Takuya Uehara, Hiroshi Doi, Kazuki Ishikawa, Masahiro Inada, Saori Tatsuno, Yutaro Wada, Yasuo Oguma, Hisato Kawakami, Kiyoshi Nakamatsu, Makoto Hosono, Yasumasa Nishimura

Head & neck　43　(10)　3132-3141　2021年7月15日

DOI： 10.1002/hed.26814 　

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BACKGROUND: The present study aimed to evaluate the prognostic factors in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal cancer (OPC) treated with definitive radiotherapy. METHODS: We retrospectively evaluated 101 patients with OPC who underwent definitive radiotherapy between 2008 and 2018. RESULTS: The median follow-up period of the surviving patients was 68 months (range, 8-164 months). The 5-year overall survival rate was 69.8%. Univariate analyses revealed that poor survival was associated with male sex, smoking ≥30 pack-years, Eastern Cooperative Oncology Group performance status ≥1, tumor-node-metastasis (TNM) stage III-IV (8th edition), HPV-negativity, serum lactate dehydrogenase (LDH) ≥202, C-reactive protein/albumin ratio ≥0.15, and lymphocyte-to-monocyte ratio <2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack-years (p < 0.01) and LDH ≥202 (p = 0.02). CONCLUSIONS: The present study suggested that high LDH levels predicted poor survival after definitive radiotherapy for patients with both HPV-positive and HPV-negative OPC.
Effects of an oral elemental nutritional supplement in gastric cancer patients with adjuvant S-1 chemotherapy after gastrectomy: A multicenter, open-label, single-arm, prospective phase II study (OGSG1108)

Hiroshi Imamura, Jin Matsuyama, Kazuhiro Nishikawa, Shunji Endo, Tomono Kawase, Yutaka Kimura, Junichi Fukui, Junji Kawada, Yukinori Kurokawa, Kazumasa Fujitani, Daisuke Sakai, Hisato Kawakami, Toshimasa Tsujinaka, Toshio Shimokawa, Yoshihiro Matsubara, Taroh Satoh, Hiroshi Furukawa

ANNALS OF GASTROENTEROLOGICAL SURGERY　5　(6)　776-784　2021年7月

DOI： 10.1002/ags3.12487 　

ISSN：2475-0328
[New Treatment Strategies for BRAF Mutation-Positive Colorectal Cancer].

Hisato Kawakami, Sota Ogata

Gan to kagaku ryoho. Cancer & chemotherapy　48　(6)　787-795　2021年6月

ISSN：0385-0684

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Precision medicine, which considers the genetics of the tumor tissues and cells for selection of the most appropriate treatment strategy, has recently been developed for colorectal cancer. The BRAF mutation status in colorectal cancer has been tested, but precision medicine for BRAF-mutated tumors had not been applicable due to no approved BRAF-targeting drugs until recently. In addition, conventional standard chemotherapy for BRAF-mutated colorectal cancer show limited effectiveness, resulting in poor prognosis. Therefore, we need new drugs specific for BRAF-mutated colorectal cancer. In this review, we outline the characteristics, development, and new treatment strategies for BRAF-mutated colorectal cancer. In addition, we introduce the BEACON CRC study, which prospectively evaluated the efficacy and safety of combination therapy of encorafenib(BRAF inhibitor), binimetinib(MEK inhibitor), and cetuximab(anti-EGFR antibody)in patients with metastatic colorectal cancer with the BRAF V600E-mutation.
Clinical Application of the FoundationOne CDx Assay to Therapeutic Decision-Making for Patients with Advanced Solid Tumors. 国際誌

Masayuki Takeda, Takayuki Takahama, Kazuko Sakai, Shigeki Shimizu, Satomi Watanabe, Hisato Kawakami, Kaoru Tanaka, Chihiro Sato, Hidetoshi Hayashi, Yoshikane Nonagase, Kimio Yonesaka, Naoki Takegawa, Tatsuya Okuno, Takeshi Yoshida, Soichi Fumita, Shinichiro Suzuki, Koji Haratani, Kazumasa Saigoh, Akihiko Ito, Tetsuya Mitsudomi, Hisashi Handa, Kazuya Fukuoka, Kazuhiko Nakagawa, Kazuto Nishio

The oncologist　26　(4)　e588-e596　2021年4月

DOI： 10.1002/onco.13639 　

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BACKGROUND: Implementation of personalized medicine requires the accessibility of tumor molecular profiling in order to allow prioritization of appropriate targeted therapies for individual patients. Our aim was to study the role of comprehensive genomic profiling assays that may inform treatment recommendations for patients with solid tumors. MATERIALS AND METHODS: We performed a prospective study to evaluate the feasibility of application of the FoundationOne CDx panel-which detects substitutions, insertions and deletions, and copy number alterations in 324 genes, select gene rearrangements, and genomic signatures including microsatellite instability and tumor mutation burden (TMB)-to patients with advanced or recurrent solid tumors before its approval in Japan. RESULTS: A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%. The median turnaround time was 41 days (range, 21-126 days). The most common known or likely pathogenic variants were TP53 mutations (n = 113), PIK3CA mutations (n = 33), APC mutations (n = 32), and KRAS mutations (n = 29). Among the 153 patients assessed for TMB, the median TMB was 4 mutations/Mb, and tumors with a high TMB (≥10 mutations/Mb) were more prevalent for lung cancer (11/32) than for other solid tumor types (9/121, Fisher's exact test p < .01). No clear trend toward increased efficacy for immune checkpoint inhibitor (ICI) monotherapy or ICI combination chemotherapy in patients with a high programmed cell death-ligand 1 tumor proportion score or a high TMB was apparent. Among the 174 patients found to harbor known or likely pathogenic actionable alterations, 24 individuals (14%) received matched targeted therapy. CONCLUSION: The FoundationOne CDx assay was performed with formalin-fixed, paraffin-embedded tumor specimens with a success rate of >95%. Such testing may inform the matching of patients with cancer with investigational or approved targeted drugs. IMPLICATIONS FOR PRACTICE: This prospective cohort study was initiated to investigate the feasibility and utility of clinical application of FoundationOne CDx. A total of 181 samples were processed for genomic testing between September 2018 and June 2019, with data being successfully obtained for 175 of these samples, yielding a success rate of 96.7%, and 24 individuals (14%) received matched targeted therapy.
胃癌周術期薬物治療の挑戦 cSS/SE N1-3 M0胃癌に対する周術期capecitabine plus oxaliplatin(CapeOx)療法の第II相試験(A phase II study of perioperative CapeOx for clinical SS/SE N1-3 M0 gastric cancer(OGSG1601))

赤丸祐介, 松山仁, 寺澤哲司, 後藤昌弘, 川端良平, 遠藤俊治, 川上尚人, 黒川幸典, 下川敏雄, 坂井大介, 藤谷和正, 佐藤太郎

日本胃癌学会総会記事　93回　208-208　2021年3月
出版者・発行元： (一社)日本胃癌学会
Docetaxel plus S-1 versus cisplatin plus S-1 in unresectable gastric cancer without measurable lesions: a randomized phase II trial (HERBIS-3).

Yukinori Kurokawa, Jin Matsuyama, Kazuhiro Nishikawa, Atsushi Takeno, Yutaka Kimura, Kazumasa Fujitani, Ryohei Kawabata, Yoichi Makari, Tetsuji Terazawa, Hisato Kawakami, Daisuke Sakai, Toshio Shimokawa, Taroh Satoh

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association　24　(2)　428-434　2021年3月

DOI： 10.1007/s10120-020-01112-1 　

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BACKGROUND: Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. METHODS: Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80-120 mg on days 1-14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80-120 mg on days 1-21, every 5 weeks). The primary endpoint was overall survival (OS). RESULTS: All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2-49) with DS and 5.5 (range 1-10) with CS. There were no treatment-related deaths. The most common grade 3-4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337-1.128), indicating non-inferiority of DS to CS with respect to OS (P < 0.001). CONCLUSIONS: DS showed slightly but nonsignificantly less toxicity and higher efficacy than CS for AGC without measurable lesions. DS should be further investigated in phase III trials.
REVIVE study: a prospective observational study in chemotherapy after nivolumab therapy for advanced gastric cancer. 国際誌

Yukiya Narita, Hirokazu Shoji, Sadayuki Kawai, Takuro Mizukami, Michio Nakamura, Toshikazu Moriwaki, Takeharu Yamanaka, Yu Sunakawa, Hisato Kawakami, Tomohiro Nishina, Toshihiro Misumi, Kei Muro

Future oncology (London, England)　17　(8)　869-875　2021年3月

DOI： 10.2217/fon-2020-0621 　

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Nivolumab is an increasingly used standard care treatment for heavily pretreated patients with advanced gastric cancer, with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown the objective response rate to cytotoxic chemotherapy potentially improves after an exposure to immune checkpoint inhibitors. Based on these data, we conducted the multicenter observational REVIVE study to evaluate the efficacy and safety of cytotoxic chemotherapy in nivolumab-refractory or nivolumab-intolerant patients with advanced gastric cancer. Patients who are refractory or intolerant to nivolumab and scheduled to receive irinotecan monotherapy, oxaliplatin combination treatment or oral trifluridine/tipiracil hydrochloride therapy will be included. The primary end point is overall survival of nivolumab-pretreated patients with advanced gastric cancer after the cytotoxic chemotherapy. Clinical trial registration: UMIN000032182 (umin.ac.jp).
Nintedanib promotes antitumour immunity and shows antitumour activity in combination with PD-1 blockade in mice: potential role of cancer-associated fibroblasts. 国際誌

Ryoji Kato, Koji Haratani, Hidetoshi Hayashi, Kazuko Sakai, Hitomi Sakai, Hisato Kawakami, Kaoru Tanaka, Masayuki Takeda, Kimio Yonesaka, Kazuto Nishio, Kazuhiko Nakagawa

British journal of cancer　124　(5)　914-924　2021年3月
出版者・発行元： Springer Science and Business Media {LLC}
DOI： 10.1038/s41416-020-01201-z 　

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BACKGROUND: Cancer-associated fibroblasts (CAFs) in the tumour microenvironment (TME) suppress antitumour immunity, and the tyrosine kinase inhibitor nintedanib has antifibrotic effects. METHODS: We performed a preclinical study to evaluate whether nintedanib might enhance antitumour immunity by targeting CAFs and thereby improve the response to immune checkpoint blockade (ICB). RESULTS: Whereas nintedanib did not suppress the growth of B16-F10 melanoma cells in vitro, it prolonged survival in a syngeneic mouse model of tumour formation by these cells, suggestive of an effect on the TME without direct cytotoxicity. Gene expression profiling indeed showed that nintedanib influenced antitumour immunity and fibrosis. Tumoural infiltration of CD8+ T cells and granzyme B production were increased by nintedanib, and its antitumour activity was attenuated by antibody-mediated depletion of these cells, indicating that nintedanib suppressed tumour growth in a CD8+ T cell-dependent manner. Moreover, nintedanib inhibited the proliferation and activation of fibroblasts. Finally, the combination of nintedanib with ICB showed enhanced antitumour efficacy in B16-F10 tumour-bearing mice. CONCLUSIONS: Our results suggest that nintedanib targeted CAFs and thereby attenuated the immunosuppressive nature of the TME and promoted the intratumoural accumulation and activation of CD8+ T cells, with these effects contributing to enhanced antitumour activity in combination with ICB.
Phase II Study of Panitumumab Monotherapy in Chemotherapy-Naïve Frail or Elderly Patients with Unresectable RAS Wild-Type Colorectal Cancer: OGSG 1602. 国際誌

Tetsuji Terazawa, Takeshi Kato, Masahiro Goto, Katsuya Ohta, Shingo Noura, Hironaga Satake, Yoshinori Kagawa, Hisato Kawakami, Hiroko Hasegawa, Kazuhiro Yanagihara, Tatsushi Shingai, Ken Nakata, Masahito Kotaka, Masayuki Hiraki, Ken Konishi, Shiro Nakae, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

The oncologist　26　(1)　17-e47　2021年1月

DOI： 10.1002/ONCO.13523 　

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LESSONS LEARNED: Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild-type unresectable colorectal cancer. It is especially effective for left-sided tumors; therefore, panitumumab as first-line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin-based or irinotecan-based combination regimens. BACKGROUND: First-line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy-naïve frail or elderly patients with unresectable RAS wild-type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first-line treatment. METHODS: We conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities. RESULTS: Thirty-six patients (median age: 81 [range, 67-88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty-three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty-eight patients (77.8%) had left-sided CRC, whereas eight (22.2%) had right-sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4-67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5-87.7). The RR of patients with left- and right-sided tumors was 65.4% (95% CI, 44.3-82.8) and 0.0% (95% CI, 0.0-36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%). CONCLUSION: Panitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.
FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer. 国際誌

Hiroko Hasegawa, Hiroya Taniguchi, Yoshiaki Nakamura, Takeshi Kato, Satoshi Fujii, Hiromichi Ebi, Manabu Shiozawa, Satoshi Yuki, Toshiki Masuishi, Ken Kato, Naoki Izawa, Toshikazu Moriwaki, Eiji Oki, Yoshinori Kagawa, Tadamichi Denda, Tomohiro Nishina, Akihito Tsuji, Hiroki Hara, Taito Esaki, Tomohiro Nishida, Hisato Kawakami, Yasutoshi Sakamoto, Izumi Miki, Wataru Okamoto, Kentaro Yamazaki, Takayuki Yoshino

Cancer science　112　(1)　314-322　2021年1月

DOI： 10.1111/cas.14693 　

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FMS-like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co-altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co-alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non-FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted.
Nivolumab versus chemotherapy in Japanese patients with advanced esophageal squamous cell carcinoma: a subgroup analysis of a multicenter, randomized, open-label, phase 3 trial (ATTRACTION-3).

Masanobu Takahashi, Ken Kato, Morihito Okada, Keisho Chin, Shigenori Kadowaki, Yasuo Hamamoto, Yuichiro Doki, Yutaro Kubota, Hisato Kawakami, Takashi Ogata, Hiroki Hara, Manabu Muto, Yuichiro Nakashima, Ryu Ishihara, Masahiro Tsuda, Satoru Motoyama, Mamoru Kodani, Yuko Kitagawa

Esophagus : official journal of the Japan Esophageal Society　18　(1)　90-99　2021年1月

DOI： 10.1007/s10388-020-00794-x 　

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BACKGROUND: The efficacy and safety of nivolumab versus chemotherapy was evaluated in the Japanese subpopulation from the overall intent-to-treat (ITT) population of the ATTRACTION-3 trial conducted in patients with advanced esophageal squamous cell carcinoma (ESCC) as second-line treatment. METHODS: Data from Japanese patients enrolled in the multicenter, randomized, open-label, phase 3 ATTRACTION-3 trial were analyzed. The primary endpoint was overall survival (OS). Secondary endpoints included duration of response (DOR), objective response rate (ORR), disease control rate (DCR), and safety. Exploratory subgroup analyses evaluated the association between OS and stratification factors/baseline variables. RESULTS: Overall, 274 (nivolumab, 136; chemotherapy, 138) of the 419 patients in ATTRACTION-3 were enrolled from Japan: response-evaluable population (107; 108) and safety population (135; 138). OS tended to be longer in the nivolumab group versus the chemotherapy group (median: 13.4 months vs. 9.4 months; HR, 0.77; 95% CI 0.59-1.01). Median DOR was longer in the nivolumab group (7.6 months) versus the chemotherapy group (3.6 months). ORRs were similar between the nivolumab [22.4% of patients (24/107)] and chemotherapy groups [22.2% (24/108); odds ratio, 0.98; 95% CI 0.52-1.87]. DCR was lower in the nivolumab group [41.1% (44/107)] versus the chemotherapy group [66.7% (72/108)]. OS in the exploratory analysis consistently favored the nivolumab group versus the chemotherapy group. Overall, nivolumab demonstrated favorable efficacy and safety versus chemotherapy in the Japanese subpopulation, and the trend was similar to that observed in the overall ATTRACTION-3 ITT population. CONCLUSION: Nivolumab represents a new standard second-line treatment option for Japanese patients with advanced ESCC.
Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021.

Masakazu Yamamoto, Masahiro Yoshida, Junji Furuse, Keiji Sano, Masayuki Ohtsuka, Shingo Yamashita, Toru Beppu, Yukio Iwashita, Keita Wada, Takako Eguchi Nakajima, Katsunori Sakamoto, Koichi Hayano, Yasuhisa Mori, Koji Asai, Ryusei Matsuyama, Teijiro Hirashita, Taizo Hibi, Nozomu Sakai, Tsutomu Tabata, Hisato Kawakami, Hiroyuki Takeda, Takuro Mizukami, Masato Ozaka, Makoto Ueno, Yoichi Naito, Naohiro Okano, Takayuki Ueno, Susumu Hijioka, Satoru Shikata, Tomohiko Ukai, Steven Strasberg, Michael G Sarr, Palepu Jagannath, Tsann-Long Hwang, Ho-Seong Han, Yoo-Seok Yoon, Hee Jung Wang, Shao-Ciao Luo, René Adam, Mariano Gimenez, Olivier Scatton, Do-Youn Oh, Tadahiro Takada

Journal of hepato-biliary-pancreatic sciences　28　(1)　1-25　2021年1月

DOI： 10.1002/jhbp.868 　

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BACKGROUND: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.
Efficacy of Combination Chemotherapy Using a Novel Oral Chemotherapeutic Agent, FTD/TPI, with Ramucirumab Murine Version DC101 in a Mouse Syngeneic Cancer Transplantation Model. 国際誌

Kenta Tsunekuni, Hisato Kawakami, Kazuaki Matsuoka, Hideki Nagase, Seiichiro Mitani, Kazuhiko Nakagawa

Journal of clinical medicine　9　(12)　2020年12月15日

DOI： 10.3390/jcm9124050 　

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Trifluridine/tipiracil (FTD/TPI) (a.k.a. TAS-102) is a combination drug for metastatic colorectal cancer (CRC) and severely pretreated metastatic gastric/gastroesophageal junction (GEJ) cancers, comprising FTD, a thymidine-based antineoplastic nucleoside analog, and TPI, which enhances FTD bioavailability. Herein, in KRAS mutant murine colorectal cancer CT26 syngeneic models, we investigate whether combination therapy with DC101 (a surrogate ramucirumab antibody, rat antimouse vascular endothelial growth factor receptor (VEGFR)-2 monoclonal antibody (mAb)) improves FTD/TPI efficacy. Tumor growth inhibition (TGI) on day 15 was 38.0% and 30.6% upon DC101 monotherapy and FTD/TPI monotherapy respectively, and 60.3% upon combination therapy. Tumor volume was significantly lower (p < 0.001) upon combination treatment than upon FTD/TPI or DC101 monotherapy, indicating the additive effects of FTD/TPI and DC101. DNA-incorporated FTD levels on Day 8 were significantly higher in combination therapy with FTD/TPI (for 5 consecutive days) and DC101 (on alternate days for 7days) than in FTD/TPI monotherapy. Furthermore, vascular endothelial cell-specific marker CD31 was downregulated in DC101-treated tumors on day 8. These results indicate that combination therapy with FTD/TPI and DC101 is a promising treatment alternative regardless of KRAS mutations.
A phase II trial of dose-reduced nab-paclitaxel for patients with previously treated, advanced or recurrent gastric cancer (OGSG 1302).

Shigeyuki Tamura, Hirokazu Taniguchi, Kazuhiro Nishikawa, Hiroshi Imamura, Junya Fujita, Atsushi Takeno, Jin Matsuyama, Yutaka Kimura, Junji Kawada, Motohiro Hirao, Masashi Hirota, Kazumasa Fujitani, Yukinori Kurokawa, Daisuke Sakai, Hisato Kawakami, Toshio Shimokawa, Taroh Satoh

International journal of clinical oncology　25　(12)　2035-2043　2020年12月

DOI： 10.1007/s10147-020-01768-w 　

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BACKGROUND: For unresectable or recurrent advanced gastric adenocarcinoma (AGC), tri-weekly administration of nanoparticle albumin-bound paclitaxel (nab-PTX) at 260 mg/m2 achieved a response rate of 27.8% in a phase II trial in Japan. However, frequent neutropenia and peripheral neuropathy limit its use in clinical settings. We, thus, conducted a single-arm phase II trial to investigate the efficacy and safety of a reduced dose (220 mg/m2) of tri-weekly nab-PTX. METHODS: Eligible patients included those with AGC and ECOG performance status of 0-2 who had received one or more prior chemotherapy containing fluoropyrimidine regimens. A reduced dose of nab-PTX (220 mg/m2) was administered tri-weekly. The primary endpoint was response rate (RR). Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity (RDI) and proportion of patients receiving subsequent chemotherapy. RESULTS: Among 33 patients enrolled, 32 were treated with protocol therapy. RR was 3.1% [95% confidence interval (CI), 0-16.2%], which did not reach the protocol-specified threshold (p = 0.966). DCR was 37.5% (95% CI, 21.1-56.3%). Median OS and PFS were 6.3 (95% CI, 4.4-14.2) and 2.2 (95% CI, 1.8-3.1) months, respectively. RDI was 97.8%. Twenty (62.5%) patients received subsequent chemotherapy. Toxicity was relatively mild with the most common grade ≥ 3 adverse events being neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). CONCLUSION: Tri-weekly nab-PTX with a reduced dose (220 mg/m2) is not recommended for AGC in a second-line or later setting, despite demonstrating less toxicity than at 260 mg/m2. Clinical trial registration The OGSG1302 trial was registered with UMIN-CTR as UMIN000000714.
Comparison of S-1-cisplatin every 5 weeks with capecitabine-cisplatin every 3 weeks for HER2-negative gastric cancer (recurrent after S-1 adjuvant therapy or chemotherapy-naïve advanced): pooled analysis of HERBIS-2 (OGSG 1103) and HERBIS-4A (OGSG 1105) trials.

Hisato Kawakami, Kazumasa Fujitani, Jin Matsuyama, Yusuke Akamaru, Shigeyuki Tamura, Shunji Endo, Yutaka Kimura, Youichi Makari, Takao Tamura, Naotoshi Sugimoto, Daisuke Sakai, Toshimasa Tsujinaka, Masahiro Goto, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

International journal of clinical oncology　25　(9)　1635-1643　2020年9月
出版者・発行元： Springer Science and Business Media {LLC}
DOI： 10.1007/s10147-020-01711-z 　

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BACKGROUND: We previously reported the HERBIS-4A phase II trial comparing S-1 plus cisplatin (SP) with capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2-negative advanced gastric cancer (GC). We performed a pooled analysis of HERBIS-4A and HERBIS-2, the phase II trial comparing SP with XP in HER2-negative recurrent GC patients with a recurrence-free interval after S-1 adjuvant therapy of ≥ 6 months. PATIENTS AND METHODS: Patients were randomly assigned to receive either SP [S-1 (40-60 mg twice daily for 21 days) plus cisplatin (60 mg/m2 on day 8), every 5 weeks] or XP [capecitabine (1000 mg/m2 twice daily for 14 days) plus cisplatin (80 mg/m2 on day 1), every 3 weeks]. RESULTS: In the pooled analysis, SP (n = 44-50) showed a longer progression-free survival [6.4 versus 5.1 months; hazard ratio (HR), 0.666; P = 0.062], overall survival (14.8 versus 10.6 months; HR, 0.695; P = 0.099), and time to treatment failure (4.6 versus 3.6 months; HR, 0.668; P = 0.045) as well as a higher disease control rate (86.4% versus 68.1%, P = 0.149) compared with XP (n = 47-51). A significant survival advantage for SP over XP was apparent in patients with a performance status of 0, a differentiated-type tumor histology, or a primary tumor localization to the upper portion of the stomach. CONCLUSION: Our pooled analysis supports the use of SP in the first-line setting for patients with HER2-negative advanced or recurrent GC with a recurrence-free interval of ≥ 6 months. CLINICAL TRIAL REGISTRATION: The HERBIS-2 trial was registered with UMIN-CTR as UMIN000006105.
頭頸部癌における免疫チェックポイント阻害薬後のセツキシマブ使用の有効性および安全性

三谷誠一郎, 田中薫, 鈴木慎一郎, 原谷浩司, 文田壮一, 川上尚人, 吉田健史, 林秀敏, 北野睦三, 土井勝美, 石川一樹, 西村恭昌, 中川和彦

頭頸部癌　46　(2)　218-218　2020年7月
出版者・発行元： (一社)日本頭頸部癌学会
ISSN：1349-5747

eISSN：1881-8382
Phase II study of 5-fluorouracil-leucovorin plus bevacizumab for chemotherapy-naïve older or frail patients with metastatic colorectal cancer (OGSG 0802).

Takashi Ohta, Takeshi Kato, Hisato Kawakami, Yasuhiro Miyake, Masahiro Goto, Shigeyoshi Iwamoto, Toshio Otsuji, Masato Nakamura, Naotoshi Sugimoto, Shu Okamura, Masahito Kotaka, Masaki Tsujie, Yukihiko Tokunaga, Hideyuki Mishima, Taishi Hata, Toshio Shimokawa, Yukinori Kurokawa, Taroh Satoh

International journal of clinical oncology　25　(7)　1291-1298　2020年7月

DOI： 10.1007/s10147-020-01656-3 　

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BACKGROUND: Older or frail patients are often underrepresented in clinical trials for metastatic colorectal cancer (mCRC). We here assessed the efficacy and safety of 5-fluorouracil (5-FU)-leucovorin plus bevacizumab in such patients. METHODS: The study (OGSG 0802) was designed as a single-arm, open-label, multicenter phase II trial. Eligible patients had mCRC and at least one of the following: an age of ≥ 65 years, an Eastern Cooperative Oncology Group performance status of 1 or 2, a serum albumin level of ≤ 3.5 g/dL, incompatibility with oxaliplatin or irinotecan, and a history of abdominal or pelvic radiotherapy. Patients received 5-FU (600 mg/m2) and l-leucovorin (200 mg/m2) on days 1, 8, and 15 together with bevacizumab (5 mg/kg) on days 1 and 15 every 4 weeks. The primary end point was objective response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty-one patients were enrolled and eligible. Median age was 76 years (range 56-90 years), and 51% of patients had a performance status of 0. The ORR was 36.6% [95% confidence interval (CI) 22.1-53.1%], median PFS was 9.4 months (95% CI 7.4-17.7 months), and median OS was 24.0 months (95% CI 19.9 months-not reached). The most common treatment-related adverse events of grade ≥ 3 were neutropenia (24%), anorexia (10%), leukopenia (7%), and mucositis/stomatitis (7%). There were no treatment-related deaths. CONCLUSION: Weekly 5-FU-leucovorin with biweekly bevacizumab may be a tolerable and effective treatment option for older or frail patients with mCRC.
Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study. 国際誌

Akihito Kawazoe, Kensei Yamaguchi, Hisateru Yasui, Yuji Negoro, Mizutomo Azuma, Kenji Amagai, Hiroki Hara, Hideo Baba, Masahiro Tsuda, Hisashi Hosaka, Hisato Kawakami, Takashi Oshima, Yasushi Omuro, Nozomu Machida, Taito Esaki, Kazuhiro Yoshida, Tomohiro Nishina, Yoshito Komatsu, Shi R Han, Shinichi Shiratori, Kohei Shitara

European journal of cancer (Oxford, England : 1990)　129　97-106　2020年4月

DOI： 10.1016/j.ejca.2020.02.002 　

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AIM: The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab). METHODS: This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status. RESULTS: Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%). CONCLUSIONS: SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer. TRIAL REGISTRATION: NCT03382600/JapicCTI-183829.
A Phase II Study of Perioperative Capecitabine plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601). 国際誌査読有り

Tetsuji Terazawa, Jin Matsuyama, Masahiro Goto, Ryohei Kawabata, Shunji Endo, Motohiro Imano, Shoichiro Fujita, Yusuke Akamaru, Hirokazu Taniguchi, Mitsutoshi Tatsumi, Sang-Woong Lee, Yoshitaka Kurisu, Hisato Kawakami, Yukinori Kurokawa, Toshio Shimokawa, Daisuke Sakai, Takeshi Kato, Kazumasa Fujitani, Taroh Satoh

The oncologist　25　(2)　119-e208　2020年2月

DOI： 10.1634/theoncologist.2019-0601 　

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LESSONS LEARNED: Perioperative capecitabine and oxaliplatin (CapeOx) therapy showed favorable efficacy with sufficient pathological response. Small sample size limited the statistical power of this result. Perioperative CapeOx therapy showed good feasibility. Further studies with larger sample size are required to validate this novel approach. BACKGROUND: D2 gastrectomy followed by adjuvant S-1 is the standard therapy for patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with GC. METHODS: The eligibility criteria included confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx (AC) after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to the JCGC (≥grade 1b). RESULTS: Thirty-seven pts were enrolled on CapeOx. An R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4-68.2) were demonstrated. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment. Grade 3-4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%). CONCLUSION: Perioperative CapeOx showed good feasibility and favorable efficacy with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations.
A Case of Pulmonary Tumor Thrombotic Microangiopathy Suggested by the Presence of Tumor Cells in Peripheral Blood

Yusuke Kawanaka, Hisato Kawakami, Shigeki Shimizu, Takeshi Yoshida, Hidetoshi Hayashi, Kazuto Nishio, Takao Satou, Kazuhiko Nakagawa

Case Reports in Oncology　13　(2)　843-848　2020年

DOI： 10.1159/000508362 　

eISSN：1662-6575
Glasgow Prognostic Score (GPS) and Tumor Response as Biomarkers of Nivolumab Monotherapy in Third- or Later-line Setting for Advanced Gastric Cancer

TAKASHI KUROSAKI, HISATO KAWAKAMI, SEIICHIRO MITANI, RYOHEI KAWABATA, TAKAYUKI TAKAHAMA, YOSHIKANE NONAGASE, SOICHI FUMITA, TOMOHIRO OZAKI, YASUTAKA CHIBA, TAKAO TAMURA, KAZUHIKO NAKAGAWA

In Vivo　34　(4)　1921-1929　2020年
出版者・発行元： Anticancer Research USA Inc.
DOI： 10.21873/invivo.11989 　

ISSN：0258-851X

eISSN：1791-7549
[Neoadjuvant Triplet Combination Chemotherapy(UDON Therapy)in Esophageal Cancer Patients with Impaired Renal Function-A Retrospective Study]. 査読有り

Yutaka Kimura, Osamu Shiraishi, Mitsuru Iwama, Hiroaki Kato, Hisato Kawakami, Tatsuya Okuno, Yoko Hiraki, Atsushi Yasuda, Masayuki Shinkai, Motohiro Imano, Kazuhiko Nakagawa, Takushi Yasuda

Gan to kagaku ryoho. Cancer & chemotherapy　46　(13)　2173-2175　2019年12月

ISSN：0385-0684

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BACKGROUND: In Japan, pre-operative 5-FU and cisplatin(CDDP)(FP)combination therapy has been the standard neoadjuvant chemotherapy(NAC)for advanced resectable esophageal cancer(EC); furthermore, the efficacy of the docetaxel (DTX)-containing triplet regimen, FP plus DTX, has been reported. However, patients with impaired renal function should not receive high-dose CDDP. We have been developing a non-CDDP-containing triplet regimen, comprising 5-FU, DTX, and nedaplatin(NED)(UDON), on a phase Ⅰ/Ⅱtrial basis. This retrospective study aimed to investigate the safety and efficacy of NAC with UDON in advanced EC patients with impaired renal function. METHODS: Five patients with advanced resectable EC with impaired renal function were enrolled in this study. Patients received NAC(5-FU, 640mg/m / 2, days 1-5; DTX, 28 mg/m2, days 1 and 15; and NED, 72mg/m2, day 1, q28, 2 courses); following this, they underwent esophagectomy. The primary endpoint was response rate, and the secondary endpoint was adverse event(AE). RESULTS: The median age was 79 years (range: 58-80 years). The ECOG performance status was 1/2 : 3/2. The main tumor locations were Ce/Ut/Mt : 1/1/3 and the cStages were ⅡA/ⅢA/ⅢC : 1/2/2. The RR(CR/PR/SD/PD : 0/4/1/0)was 80%. The pathological response was grade 1a/1b : 2/3. Major grade 3 or 4 AEs included neutropenia(40%), febrile neutropenia(20%), diarrhea(20%), and hyponatremia( 40%). There was no treatment-related death or reoperation. CONCLUSIONS: NAC with UDON might be feasible and effective in patients with advanced resectable EC with impaired renal function, who are ineligible for high-dose CDDP administration. We are planning a phaseⅡclinical study based on the present results.
U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation. 国際誌査読有り

Haratani K, Yonesaka K, Takamura S, Maenishi O, Kato R, Takegawa N, Kawakami H, Tanaka K, Hayashi H, Takeda M, Maeda N, Kagari T, Hirotani K, Tsurutani J, Nishio K, Doi K, Miyazawa M, Nakagawa K

The Journal of clinical investigation　130　(1)　374-388　2019年10月
出版者・発行元：
DOI： 10.1172/JCI126598 　

ISSN：0021-9738
A Phase II Study of Perioperative Capecitabine Plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601). 国際誌査読有り

Tetsuji Terazawa, Jin Matsuyama, Masahiro Goto, Ryohei Kawabata, Shunji Endo, Motohiro Imano, Shoichiro Fujita, Yusuke Akamaru, Hirokazu Taniguchi, Mitsutoshi Tatsumi, Sang-Woong Lee, Yoshitaka Kurisu, Hisato Kawakami, Yukinori Kurokawa, Toshio Shimokawa, Daisuke Sakai, Takeshi Kato, Kazumasa Fujitani, Taroh Satoh

The oncologist　2019年9月30日

DOI： 10.1634/theoncologist.2019-0601 　

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LESSONS LEARNED: Perioperative capecitabine and oxaliplatin (CapeOx) therapy showed favorable efficacy with sufficient pathological response. Small sample size limited the statistical power of this result.Perioperative CapeOx therapy showed good feasibility.Further studies with larger sample size are required to validate this novel approach. BACKGROUND: D2 gastrectomy followed by adjuvant S-1 is the standard therapy for patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with GC. METHODS: The eligibility criteria included confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx (AC) after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to the JCGC (≥grade 1b). RESULTS: Thirty-seven pts were enrolled on CapeOx. An R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4-68.2) were demonstrated. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment. Grade 3-4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%). CONCLUSION: Perioperative CapeOx showed good feasibility and favorable efficacy with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations.
Aberrant HER3 ligand heregulin-expressing head and neck squamous cell carcinoma is resistant to anti-EGFR antibody cetuximab, but not second-generation EGFR-TKI. 国際誌査読有り

Yonesaka K, Tanaka K, Kitano M, Kawakami H, Hayashi H, Takeda M, Sakai K, Nishio K, Doi K, Nakagawa K

Oncogenesis　8　(10)　54-54　2019年9月
出版者・発行元：
DOI： 10.1038/s41389-019-0164-9 　
Clinical and immune profiling for cancer of unknown primary site. 国際誌査読有り

Haratani K, Hayashi H, Takahama T, Nakamura Y, Tomida S, Yoshida T, Chiba Y, Sawada T, Sakai K, Fujita Y, Togashi Y, Tanizaki J, Kawakami H, Ito A, Nishio K, Nakagawa K

Journal for immunotherapy of cancer　7　(1)　251-251　2019年9月

DOI： 10.1186/s40425-019-0720-z 　
A comparative study of curated contents by knowledge-based curation system in cancer clinical sequencing. 国際誌査読有り

Sakai K, Takeda M, Shimizu S, Takahama T, Yoshida T, Watanabe S, Iwasa T, Yonesaka K, Suzuki S, Hayashi H, Kawakami H, Nonagase Y, Tanaka K, Tsurutani J, Saigoh K, Ito A, Mitsudomi T, Nakagawa K, Nishio K

Scientific reports　9　(1)　11340-11340　2019年8月

DOI： 10.1038/s41598-019-47673-9 　
DELIVER (JACCRO GC-08) trial: discover novel host-related immune-biomarkers for nivolumab in advanced gastric cancer. 国際誌

Yu Sunakawa, Eisuke Inoue, Ryo Matoba, Hisato Kawakami, Yoshiharu Sato, Takako Eguchi Nakajima, Kei Muro, Wataru Ichikawa, Masashi Fujii

Future oncology (London, England)　15　(21)　2441-2447　2019年7月

DOI： 10.2217/fon-2019-0167 　

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Aim: Nivolumab has survival benefit in patients with previously treated advanced gastric cancer; however, about 60% of the patients did not respond to nivolumab, raising the necessity of its predictive biomarkers. Gut microbiome has been shown to be associated with efficacy of anti-PD-1 antibody in various types of cancers, but little is known about gastric cancer. Design: This is an observational/translational study to evaluate clinical outcomes of nivolumab and to discover novel immune-related biomarkers (gut microbiome, genetic polymorphism, gene expression and metabolome in plasma) in gastric cancer, using fecal and blood samples at two points before and after treatment. Candidate factors will be explored in first 200 patients and then validated in last 300 patients. Trial registration: UMIN000030850.
Microsatellite instability status in metastatic colorectal cancer and effect of immune checkpoint inhibitors on survival in MSI-high metastatic colorectal cancer.

Okamoto, Wataru, Nakamura, Yoshiaki, Shiozawa, Manabu, Komatsu, Yoshito, Denda, Tadamichi, Hara, Hiroki, Kagawa, Yoshinori, Narita, Yukiya, Kawakami, Hisato, Esaki, Taito, Nishina, Tomohiro, Izawa, Naoki, Ando, Koji, Moriwaki, Toshikazu, Kato, Takeshi, Nagashima, Fumio, Satoh, Taroh, Nomura, Shogo, Yoshino, Takayuki, Akagi, Kiwamu

JOURNAL OF CLINICAL ONCOLOGY　37　(15::S)　2019年5月
出版者・発行元： AMER SOC CLINICAL ONCOLOGY
DOI： 10.1200/JCO.2019.37.15_suppl.e15106 　

ISSN：0732-183X
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. 国際誌

K Muro, F Lordick, T Tsushima, G Pentheroudakis, E Baba, Z Lu, B C Cho, I M Nor, M Ng, L-T Chen, K Kato, J Li, M-H Ryu, W I Wan Zamaniah, W-P Yong, K-H Yeh, T E Nakajima, K Shitara, H Kawakami, Y Narita, T Yoshino, E Van Cutsem, E Martinelli, E C Smyth, D Arnold, H Minami, J Tabernero, J-Y Douillard

Annals of oncology : official journal of the European Society for Medical Oncology　30　(1)　34-43　2019年1月1日

DOI： 10.1093/annonc/mdy498 　

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The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. 国際誌

K Muro, E Van Cutsem, Y Narita, G Pentheroudakis, E Baba, J Li, M-H Ryu, W I Wan Zamaniah, W-P Yong, K-H Yeh, K Kato, Z Lu, B C Cho, I M Nor, M Ng, L-T Chen, T E Nakajima, K Shitara, H Kawakami, T Tsushima, T Yoshino, F Lordick, E Martinelli, E C Smyth, D Arnold, H Minami, J Tabernero, J-Y Douillard

Annals of oncology : official journal of the European Society for Medical Oncology　30　(1)　19-33　2019年1月1日

DOI： 10.1093/annonc/mdy502 　

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The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
Targeting of the HER2/HER3 signaling axis overcomes ligand-mediated resistance to trastuzumab in HER2-positive breast cancer. 国際誌査読有り

Watanabe S, Yonesaka K, Tanizaki J, Nonagase Y, Takegawa N, Haratani K, Kawakami H, Hayashi H, Takeda M, Tsurutani J, Nakagawa K

Cancer Med　8　(1258)　1268-1268　2019年

DOI： 10.1002/cam4.1995 　
Phase II Trial of 5-Fluorouracil, Docetaxel, and Nedaplatin (UDON) Combination Therapy for Recurrent or Metastatic Esophageal Cancer. 国際誌査読有り

Ueda H, Kawakami H, Nonagase Y, Takegawa N, Okuno T, Takahama T, Takeda M, Chiba Y, Tamura T, Nakagawa K

Oncotarget　24　(2)　163　2019年

DOI： 10.1634/theoncologist.2018-0653 　
[A Case of Advanced Esophageal Cancer Successfully Treated with Neoadjuvant Chemotherapy Containing 5-FU, Docetaxel. and Nedaplatin Combination Therapy]. 査読有り

Kimura Y, Shiraishi O, Kawakami H, Ueda H, Okuno T, Hiraki Y, Kato H, Iwama M, Yasuda A, Shinkai M, Chikugo T, Imano M, Imamoto H, Nakagawa K, Yasuda T

Gan to kagaku ryoho. Cancer & chemotherapy　45　(13)　1812-1814　2018年12月

ISSN：0385-0684
Randomized, Open-Label Phase II Study Comparing Capecitabine-Cisplatin Every 3 Weeks with S-1-Cisplatin Every 5 Weeks in Chemotherapy-Naïve Patients with HER2-Negative Advanced Gastric Cancer: OGSG1105, HERBIS-4A Trial. 国際誌査読有り

Kawakami H, Takeno A, Endo S, Makari Y, Kawada J, Taniguchi H, Tamura S, Sugimoto N, Kimura Y, Tamura T, Fujitani K, Sakai D, Shimokawa T, Kurokawa Y, Satoh T

The oncologist　23　(12)　1411-e147-e147　2018年12月
出版者・発行元：
DOI： 10.1634/theoncologist.2018-0175 　

ISSN：1083-7159
Mutational activation of the epidermal growth factor receptor down-regulates major histocompatibility complex class I expression via the extracellular signal-regulated kinase in non-small cell lung cancer. 国際誌査読有り

Watanabe S, Hayashi H, Haratani K, Shimizu S, Tanizaki J, Sakai K, Kawakami H, Yonesaka K, Tsurutani J, Togashi Y, Nishio K, Ito A, Nakagawa K

Cancer science　110　(1)　52-60　2018年11月

DOI： 10.1111/cas.13860 　

ISSN：1347-9032
腎機能低下を伴う進行食道癌患者に対する安全な3剤併用術前化学療法(UDON療法)

木村豊, 白石治, 川上尚人, 奥野達哉, 岩間密, 加藤寛章, 平木洋子, 安田篤, 新海政幸, 今野元博, 中川和彦, 安田卓司

日本癌治療学会学術集会抄録集　56回　P72-5　2018年10月
出版者・発行元： (一社)日本癌治療学会
An HER3-targeting antibody-drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC. 国際誌査読有り

Yonesaka K, Takegawa N, Watanabe S, Haratani K, Kawakami H, Sakai K, Chiba Y, Maeda N, Kagari T, Hirotani K, Nishio K, Nakagawa K

Oncogene　38　(9)　1398-1409　2018年10月

DOI： 10.1038/s41388-018-0517-4 　

ISSN：0950-9232
治療抵抗性であった免疫関連性大腸炎に対して人工肛門造設術が有効であった1例査読有り

大東弘治, 上田和毅, 川村純一郎, 牛嶋北斗, 家根由典, 吉岡康多, 所忠男, 肥田仁一, 川上尚人, 奥野清隆

日本大腸肛門病学会雑誌　71　(抄録号)　A124-A124　2018年9月
出版者・発行元： (一社)日本大腸肛門病学会
ISSN：0047-1801

eISSN：1882-9619
Nivolumab-Induced Hemophilia A Presenting as Gastric Ulcer Bleeding in a Patient With NSCLC. 国際誌査読有り

Kato R, Hayashi H, Sano K, Handa K, Kumode T, Ueda H, Okuno T, Kawakami H, Matsumura I, Kudo M, Nakagawa K

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer　13　(12)　e239-e241　2018年7月

DOI： 10.1016/j.jtho.2018.06.024 　

ISSN：1556-0864
Nivolumab-induced acute granulomatous tubulointerstitial nephritis in a patient with gastric cancer 国際誌査読有り

Yoshihisa Nakatani, Hisato Kawakami, Masashi Ichikawa, Sachiyo Yamamoto, Yasuo Otsuka, Akiko Mashiko, Yasutoshi Takashima, Akihiko Ito, Kazuhiko Nakagawa, Shuji Arima

Investigational New Drugs　36　(4)　1-6　2018年4月6日
出版者・発行元： Springer New York LLC
DOI： 10.1007/s10637-018-0596-7 　

ISSN：1573-0646 0167-6997
Targeting CDK1 and MEK/ERK Overcomes Apoptotic Resistance in BRAF-Mutant Human Colorectal Cancer. 国際誌査読有り

Zhang P, Kawakami H, Liu W, Zeng X, Strebhardt K, Tao K, Huang S, Sinicrope FA

Molecular cancer research : MCR　16　(3)　378-389　2018年3月

DOI： 10.1158/1541-7786.MCR-17-0404 　

ISSN：1541-7786
Analysis of RAS/BRAF mutations in a randomized phase II WJOG6510G study of panitumumab plus irinotecan versus cetuximab plus irinotecan in chemorefractory metastatic colorectal cancer. 査読有り

Nishina Tomohiro, Taniguchi Hiroya, Sakai Daisuke, Kawakami Hisato, Sugimoto Naotoshi, Hara Hiroki, Esaki Taito, Denda Tadamichi, Makiyama Akitaka, Tsuda Masahiro, Okuda Hiroyuki, Izawa Naoki, Hosokawa Ayumu, Yamazaki Kentaro, Tokunaga Shinya, Moriwaki Toshikazu, Tsuji Akihito, Koh Yasuhiro, Kishimoto Junji, Muro Kei

JOURNAL OF CLINICAL ONCOLOGY　36　(4)　2018年2月1日

DOI： 10.1200/JCO.2018.36.4_suppl.624 　

ISSN：0732-183X

eISSN：1527-7755
Two-step Intensity-modulated Radiation Therapy for Oropharyngeal Cancer: Initial Clinical Experience and Validation of Clinical Staging. 国際誌査読有り

Hitoshi Tatebe, Hiroshi Doi, Kazuki Ishikawa, Hisato Kawakami, Masaki Yokokawa, Kiyoshi Nakamatsu, Shuichi Kanamori, Toru Shibata, Mutsukazu Kitano, Yasumasa Nishimura

Anticancer research　38　(2)　979-986　2018年2月

DOI： 10.21873/anticanres.12312 　

ISSN：0250-7005

eISSN：1791-7530

詳細を見る詳細を閉じる

AIM: To evaluate the clinical results of two-step intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer. PATIENTS AND METHODS: Eighty patients were treated with two-step IMRT between 2002 and 2014. Whole-neck radiotherapy (44.0-50.0 Gy/22-25 fractions) was delivered by IMRT, followed by boost IMRT to the high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Forty-seven patients received concurrent chemotherapy. Immunohistochemistry for human papillomavirus type 16 (HPV/p16) was performed for 64 patients. RESULTS: The 5-year overall survival and locoregional control rates for stage I, II, III, and IVA-B disease were 80.0%, 75.0%, 78.0%, and 64.0% and 100.0%, 75.0%, 92.0%, and 82.0%, respectively. Overall survival was significantly higher in HPV/p16-positive patients than in HPV/p16-negative patients (p=0.01). Xerostomia of grade 2 or more was noted in 10 patients. CONCLUSION: Favourable overall survival and locoregional control rates with excellent salivary preservation were obtained using the two-step IMRT method for oropharyngeal cancer.
T790M-Selective EGFR-TKI Combined with Dasatinib as an Optimal Strategy for Overcoming EGFR-TKI Resistance in T790M-Positive Non-Small Cell Lung Cancer 国際誌査読有り

Satomi Watanabe, Takeshi Yoshida, Hisato Kawakami, Naoki Takegawa, Junko Tanizaki, Hidetoshi Hayashi, Masayuki Takeda, Kimio Yonesaka, Junji Tsurutani, Kazuhiko Nakagawa

MOLECULAR CANCER THERAPEUTICS　16　(11)　2563-2571　2017年11月

DOI： 10.1158/1535-7163.MCT-17-0351 　

ISSN：1535-7163

eISSN：1538-8514
Clinical evaluation of palliative chemoradiotherapy for metastatic esophageal cancer 国際誌査読有り

Hiroto Ueda, Masayuki Takeda, Shinya Ueda, Hisato Kawakami, Tatsuya Okuno, Naoki Takegawa, Hidetoshi Hayashi, Junji Tsurutani, Takao Tamura, Kazuki Ishikawa, Yasumasa Nishimura, Kazuhiko Nakagawa

ONCOTARGET　8　(46)　80286-80294　2017年10月

DOI： 10.18632/oncotarget.17925 　

ISSN：1949-2553

eISSN：1949-2553
Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer 国際誌査読有り

Hisato Kawakami, Junko Tanizaki, Kaoru Tanaka, Koji Haratani, Hidetoshi Hayashi, Masayuki Takeda, Ken Kamata, Mamoru Takenaka, Masatomo Kimura, Takaaki Chikugo, Takao Sato, Masatoshi Kudo, Akihiko Ito, Kazuhiko Nakagawa

INVESTIGATIONAL NEW DRUGS　35　(4)　529-536　2017年8月

DOI： 10.1007/s10637-017-0453-0 　

ISSN：0167-6997

eISSN：1573-0646
Abstract 2173: Targeting CDK1 and MEK/ERK overcome mutantBRAF-mediated apoptosis resistance in human colorectal cancer cells

Hisato Kawakami, Shengbing Huang, Frank A. Sinicrope

Cancer Research　77　(13 Supplement)　2173-2173　2017年7月1日
出版者・発行元： American Association for Cancer Research ({AACR})
DOI： 10.1158/1538-7445.am2017-2173 　

ISSN：0008-5472
Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer. 国際誌査読有り

Muranaka T, Kuwatani M, Komatsu Y, Sawada K, Nakatsumi H, Kawamoto Y, Yuki S, Kubota Y, Kubo K, Kawahata S, Kawakubo K, Kawakami H, Sakamoto N

Journal of gastrointestinal oncology　8　(3)　566-571　2017年6月

DOI： 10.21037/jgo.2017.02.02 　

ISSN：2078-6891
Mutant BRAF Upregulates MCL-1 to Confer Apoptosis Resistance that Is Reversed by MCL-1 Antagonism and Cobimetinib in Colorectal Cancer 国際誌査読有り

Hisato Kawakami, Shengbing Huang, Krishnendu Pal, Shamit K. Dutta, Debabrata Mukhopadhyay, Frank A. Sinicrope

MOLECULAR CANCER THERAPEUTICS　15　(12)　3015-3027　2016年12月

DOI： 10.1158/1535-7163.MCT-16-0017 　

ISSN：1535-7163

eISSN：1538-8514
Heregulin-expressing HER2-positive breast and gastric cancer exhibited heterogeneous susceptibility to the anti-HER2 agents lapatinib, trastuzumab and T-DM1 国際誌査読有り

Yoshikane Nonagase, Kimio Yonesaka, Hisato Kawakami, Satomi Watanabe, Koji Haratani, Takayuki Takahama, Naoki Takegawa, Hiroto Ueda, Junko Tanizaki, Hidetoshi Hayashi, Takeshi Yoshida, Masayuki Takeda, Yasutaka Chiba, Takao Tamura, Kazuhiko Nakagawa, Junji Tsurutani

ONCOTARGET　7　(51)　84860-84871　2016年12月

DOI： 10.18632/oncotarget.12743 　

ISSN：1949-2553
MET-targeted therapy for gastric cancer: the importance of a biomarker-based strategy 査読有り

Hisato Kawakami, Isamu Okamoto

GASTRIC CANCER　19　(3)　687-695　2016年7月

DOI： 10.1007/s10120-015-0585-x 　

ISSN：1436-3291

eISSN：1436-3305
Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors 国際誌査読有り

Toshio Shimizu, Takashi Seto, Fumihiko Hirai, Mitsuhiro Takenoyama, Kaname Nosaki, Junji Tsurutani, Hiroyasu Kaneda, Tsutomu Iwasa, Hisato Kawakami, Kazuo Noguchi, Takashi Shimamoto, Kazuhiko Nakagawa

INVESTIGATIONAL NEW DRUGS　34　(3)　347-354　2016年6月

DOI： 10.1007/s10637-016-0347-6 　

ISSN：0167-6997

eISSN：1573-0646
Molecular Biomarkers in the Personalized Treatment of Colorectal Cancer 国際誌査読有り

Frank A. Sinicrope, Koichi Okamoto, Pashtoon M. Kasi, Hisato Kawakami

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY　14　(5)　651-658　2016年5月

DOI： 10.1016/j.cgh.2016.02.008 　

ISSN：1542-3565

eISSN：1542-7714
Anti-HER3 monoclonal antibody patritumab sensitizes refractory non-small cell lung cancer to the epidermal growth factor receptor inhibitor erlotinib. 査読有り

Oncogene　35　(7)　878-886　2016年2月

DOI： 10.1038/onc.2015.142 　

ISSN：0950-9232

eISSN：1476-5594
HER3 and its Ligand, Heregulin, as Targets for Cancer Therapy 国際誌査読有り

Hisato Kawakami, Kimio Yonesaka

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY　11　(3)　267-274　2016年

DOI： 10.2174/1574892811666160418123221 　

ISSN：1574-8928

eISSN：2212-3970
Implications of mismatch repair-deficient status on management of early stage colorectal cancer. 国際誌査読有り

Kawakami H, Zaanan A, Sinicrope FA

Journal of gastrointestinal oncology　6　(6)　676-684　2015年12月

DOI： 10.3978/j.issn.2078-6891.2015.065 　

ISSN：2078-6891
The Mutant KRAS Gene Up-regulates BCL-XL Protein via STAT3 to Confer Apoptosis Resistance That Is Reversed by BIM Protein Induction and BCL-XL Antagonism 国際誌査読有り

Aziz Zaanan, Koichi Okamoto, Hisato Kawakami, Khashayarsha Khazaie, Shengbing Huang, Frank A. Sinicrope

JOURNAL OF BIOLOGICAL CHEMISTRY　290　(39)　23838-23849　2015年9月

DOI： 10.1074/jbc.M115.657833 　

ISSN：0021-9258

eISSN：1083-351X
Phase I trial of 5-FU, docetaxel, and nedaplatin (UDON) combination therapy for recurrent or metastatic esophageal cancer 国際誌査読有り

Shinya Ueda, Hisato Kawakami, Shinichi Nishina, Tsutomu Sakiyama, Yoshikane Nonagase, Takafumi Okabe, Takao Tamura, Kazuhiko Nakagawa

CANCER CHEMOTHERAPY AND PHARMACOLOGY　76　(2)　279-285　2015年8月

DOI： 10.1007/s00280-015-2799-3 　

ISSN：0344-5704

eISSN：1432-0843
Microsatellite Instability Testing and Its Role in the Management of Colorectal Cancer 国際誌査読有り

Hisato Kawakami, Aziz Zaanan, Frank A. Sinicrope

CURRENT TREATMENT OPTIONS IN ONCOLOGY　16　(7)　30-30　2015年7月

DOI： 10.1007/s11864-015-0348-2 　

ISSN：1527-2729

eISSN：1534-6277
Reversal of Mutant KRAS-Mediated Apoptosis Resistance by Concurrent Noxa/Bik Induction and Bcl-2/Bcl-xL Antagonism in Colon Cancer Cells 国際誌査読有り

Koichi Okamoto, Aziz Zaanan, Hisato Kawakami, Shengbing Huang, Frank A. Sinicrope

MOLECULAR CANCER RESEARCH　13　(4)　659-669　2015年4月

DOI： 10.1158/1541-7786.MCR-14-0476 　

ISSN：1541-7786

eISSN：1557-3125
A phase I dose-escalation study of eribulin and S-1 for metastatic breast cancer. 査読有り

Sakiyama T, Tsurutani J, Iwasa T, Kawakami H, Nonagase Y, Yoshida T, Tanaka K, Fujisaka Y, Kurata T, Komoike Y, Nishio K, Nakagawa K

Br J Cancer.　112　(5)　819-824　2015年3月

DOI： 10.1038/bjc.2015.10 　

ISSN：0007-0920

eISSN：1532-1827
The anti-HER3 antibody patritumab abrogates cetuximab resistance mediated by heregulin in colorectal cancer cells 国際誌査読有り

Hisato Kawakami, Isamu Okamoto, Kimio Yonesaka, Kunio Okamoto, Kiyoko Shibata, Yume Shinkai, Haruka Sakamoto, Michiko Kitano, Takao Tamura, Kazuto Nishio, Kazuhiko Nakagawa

ONCOTARGET　5　(23)　11847-11856　2014年12月

DOI： 10.18632/oncotarget.2663 　

ISSN：1949-2553

eISSN：1949-2553
CLINICAL BENEFIT OF CONTINUED THERAPY WITH CRIZOTINIB BEYOND INITIAL DISEASE PROGRESSION IN ADVANCED ALK POSITIVE NSCLC 査読有り

Hiroyasu Kaneda, Masayuki Takeda, Kaoru Tanaka, Takeshi Yoshida, Tsutomu Iwasa, Kunio Okamoto, Hisato Kawakami, Takayuki Takahama, Toshio Shimizu, Kazuhiko Nakagawa

ANNALS OF ONCOLOGY　25　2014年10月

DOI： 10.1093/annonc/mdu435.109 　

ISSN：0923-7534

eISSN：1569-8041
Inhibition of EGFR, HER2 and HER3 signaling with AZD8931 alone and in combination with paclitaxel: Phase I study in Japanese patients with advanced solid malignancies and advanced breast cancer 国際誌査読有り

Takayasu Kurata, Junji Tsurutani, Yasuhito Fujisaka, Wataru Okamoto, Hidetoshi Hayashi, Hisato Kawakami, Eisei Shin, Nobuya Hayashi, Kazuhiko Nakagawa

INVESTIGATIONAL NEW DRUGS　32　(5)　946-954　2014年10月

DOI： 10.1007/s10637-014-0112-7 　

ISSN：0167-6997

eISSN：1573-0646
Targeting MET Amplification as a New Oncogenic Driver 国際誌査読有り

Hisato Kawakami, Isamu Okamoto, Wataru Okamoto, Junko Tanizaki, Kazuhiko Nakagawa, Kazuto Nishio

CANCERS　6　(3)　1540-1552　2014年9月

DOI： 10.3390/cancers6031540 　

ISSN：2072-6694
Risk Factors for Cisplatin-Induced Nephrotoxicity and Potential of Magnesium Supplementation for Renal Protection 国際誌査読有り

Yasuhiro Kidera, Hisato Kawakami, Tsutomu Sakiyama, Kunio Okamoto, Kaoru Tanaka, Masayuki Takeda, Hiroyasu Kaneda, Shin-ichi Nishina, Junji Tsurutani, Kimiko Fujiwara, Morihiro Nomura, Yuzuru Yamazoe, Yasutaka Chiba, Shozo Nishida, Takao Tamura, Kazuhiko Nakagawa

PLOS ONE　9　(7)　e101902　2014年7月

DOI： 10.1371/journal.pone.0101902 　

ISSN：1932-6203
Phase I pharmacokinetic study of S-1 granules and nedaplatin for advanced head and neck cancer. 国際誌査読有り

Hidetoshi Hayashi, Isamu Okamoto, Shinya Ueda, Kaoru Tanaka, Kunio Okamoto, Hisato Kawakami, Shinichi Nishina, Masayuki Takeda, Yasuhito Fujisaka, Taroh Satoh, Kyoichi Terao, Yasumasa Nishimura, Katsumi Doi, Kazuhiko Nakagawa

Anticancer research　33　(12)　5699-705　2013年12月

ISSN：0250-7005

eISSN：1791-7530

詳細を見る詳細を閉じる

AIM: We performed a pharmacokinetic phase I trial of the combination of S-1 granules and nedaplatin for head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Patients were treated with both nedaplatin on day 1 at a dose starting at 80 mg/m(2) (level 1) escalating up to 90 mg/m(2) (level 2), and S-1 granules at a daily dose of 80 mg/m(2) on days 1 to 14 every three weeks. The primary end-point was determination of the recommended dose. RESULTS: Twenty patients were enrolled. Dose-limiting toxicities occurred in one out of six patients at dose level 1 (neutropenia) and in all three patients at level 2 (neutropenia and thrombocytopenia). The recommended dose was determined as level 1. Pharmacokinetic parameters of S-1 granule did not differ from the capsula formulation. The response rate was 42.1%. CONCLUSION: This combination was well-tolerated and manifested a promising activity against HNSCC.
Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma 国際誌査読有り

Hisato Kawakami, Isamu Okamoto, Kyoichi Terao, Kazuko Sakai, Minoru Suzuki, Shinya Ueda, Kaoru Tanaka, Kiyoko Kuwata, Yume Morita, Koji Ono, Kazuto Nishio, Yasumasa Nishimura, Katsumi Doi, Kazuhiko Nakagawa

CANCER MEDICINE　2　(6)　933-941　2013年12月

DOI： 10.1002/cam4.151 　

ISSN：2045-7634
Postprogression survival for first-line chemotherapy in patients with advanced gastric cancer 国際誌査読有り

Hisato Kawakami, Isamu Okamoto, Hidetoshi Hayashi, Masataka Taguri, Satoshi Morita, Kazuhiko Nakagawa

European Journal of Cancer　49　(14)　3003-3009　2013年9月
出版者・発行元： Elsevier {BV}
DOI： 10.1016/j.ejca.2013.05.022 　

ISSN：0959-8049 1879-0852
Phase I dose finding study of AZD8931, an inhibitor of EGFR, HER2, and HER3 signaling, alone or in combination with paclitaxel in Japanese patients. 査読有り

Fujisaka Yasuhito, Kurata Takayasu, Tsurutani Junji, Okamoto Wataru, Hayashi Hidetoshi, Kawakami Hisato, Shin Eisei, Hayashi Nobuya, Nakagawa Kazuhiko

JOURNAL OF CLINICAL ONCOLOGY　31　(15)　2013年5月20日

ISSN：0732-183X

eISSN：1527-7755
Phase I trial of OTS11101, an anti-angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor 査読有り

Hidetoshi Hayashi, Takayasu Kurata, Yasuhito Fujisaka, Hisato Kawakami, Kaoru Tanaka, Takafumi Okabe, Masayuki Takeda, Taroh Satoh, Koji Yoshida, Takuya Tsunoda, Tokuzo Arao, Kazuto Nishio, Kazuhiko Nakagawa

CANCER SCIENCE　104　(1)　98-104　2013年1月

DOI： 10.1111/cas.12034 　

ISSN：1349-7006
Practical Use of Gemcitabine and Cisplatin Combination Therapy as First-Line Treatment for Japanese Patients with Advanced Biliary Tract Cancer 査読有り

Kawakami H, Okamoto I, Okamoto W, Takeda M, Ueda S, Kudo T, Nishina S, Fujisaka Y, Miyazaki M, Tsurutani J, Kurata T, Nakagawa K

Journal of Cancer Therapy　4　1068-1073　2013年
Phase I trial of OTS11101, an anti-angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor. 国際誌査読有り

Hidetoshi Hayashi, Takayasu Kurata, Yasuhito Fujisaka, Hisato Kawakami, Kaoru Tanaka, Takafumi Okabe, Masayuki Takeda, Taroh Satoh, Koji Yoshida, Takuya Tsunoda, Tokuzo Arao, Kazuto Nishio, Kazuhiko Nakagawa

Cancer science　104　(1)　98-104　2013年1月

DOI： 10.1111/cas.12034 　

ISSN：1347-9032

詳細を見る詳細を閉じる

OTS11101 is a novel peptide vaccine that acts as an angiogenesis inhibitor by inducing cytotoxic T lymphocyte (CTL) cells that specifically target vascular endothelial cells expressing vascular endothelial growth factor (VEGF) receptor 1. We conducted a phase I study to evaluate the safety, tolerability, maximum tolerated dose, and pharmacodynamic biomarker status of this vaccine. Nine patients with advanced solid tumors received 1.0, 2.0, or 3.0 mg of OTS11101 subcutaneously, once a week in a 28-day cycle. Three patients experienced grade 1 injection site reactions, which were the most frequent adverse events. Grade 2 proteinuria and hypertension each occurred in one patient. As other toxicities were generally mild, the maximum tolerated dose was not reached. Furthermore, we explored the induction of specific activated CTLs, and biomarkers related to angiogenesis. A pharmacodynamics study revealed that induction of specific CTLs was observed for a dose of 2.0 and 3.0 mg. The serum concentrations of soluble VEGF receptor 1 and 2 after vaccination increased significantly compared with baseline. A microarray was performed to give a comprehensive analysis of gene expression, suggesting that OTS11101 vaccination resulted in T cell activation in a clinical setting. In conclusion, OTS11101 was well tolerated in patients up to 3.0 mg once weekly and our biomarker analysis suggested that this anti-angiogenesis vaccine is biologically active.
MET amplification as a potential therapeutic target in gastric cancer 国際誌査読有り

Hisato Kawakami, Isamu Okamoto, Tokuzo Arao, Wataru Okamoto, Kazuko Matsumoto, Hirokazu Taniguchi, Kiyoko Kuwata, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa, Yasuhide Yamada

ONCOTARGET　4　(1)　9-17　2013年1月

DOI： 10.18632/oncotarget.718 　

ISSN：1949-2553

eISSN：1949-2553
Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy. 国際誌査読有り

Takeda M, Okamoto I, Sakai K, Kawakami H, Nishio K, Nakagawa K

Ann Oncol　23　(11)　2931-2936　2012年11月

DOI： 10.1093/annonc/mds124 　
CHEMOTHERAPY WITH CPT-11 AFTER GEMCITABINE FAILURE IN PATIENTS WITH ADVANCED PANCREATIC CANCER 査読有り

Kaneda Hiroyasu, Ueda Shinya, Makimura Chihiro, Kiyota Hidemi, Kawakami Hisato, Okamoto Isamu, Tanaka Kaoru, Nishina Shinichi, Kudo Toshihiro, Turutani Junji, Miyazaki Masaki, Fujisaka Yasuhito, Okamoto Wataru, Kurata Takayasu, Nakagawa Kazuhiko

ANNALS OF ONCOLOGY　23　65-65　2012年6月

ISSN：0923-7534
SECOND-LINE CHEMOTHERAPY WITH S-1 AFTER CISPLATIN AND GEMCITABINE FAILURE IN PATIENTS WITH ADVANCED BILIARY TRACT CANCER 査読有り

Ueda Shinya, Kawakami Hisato, Okamoto Wataru, Nishina Shinichi, Kudo Toshihiro, Makimura Chihiro, Kiyota Hidemi, Tanaka Kaoru, Kaneda Hiroyasu, Fujisaka Yasuhito, Miyazaki Masaki, Turutani Junji, Okamoto Isamu, Kurata Takayasu, Nakagawa Kazuhiko

ANNALS OF ONCOLOGY　23　65-65　2012年6月

ISSN：0923-7534
Capecitabine plus Cisplatin treatment for advanced gastric cancer in a patient with hepatic impairment secondary to metastases. 国際誌査読有り

Kawakami H, Nishina S, Ueda S, Kudo T, Okamoto W, Kurata T, Okamoto I, Nakagawa K

Gastrointestinal cancer research : GCR　5　(3)　103-105　2012年5月

ISSN：1934-7820

eISSN：1934-7987
XP療法が有効であった黄疸を伴う高度肝障害を有する進行胃癌の1症例

川上尚人, 仁科慎一, 上田眞也, 工藤敏啓, 岡本渉, 鶴谷純司, 倉田宝保, 岡本勇, 中川和彦

日本胃癌学会総会記事　84回　339-339　2012年2月
出版者・発行元： (一社)日本胃癌学会
Human Epidermal Growth Factor Eyedrops for Cetuximab-Related Filamentary Keratitis 国際誌査読有り

Hisato Kawakami, Koji Sugioka, Kimio Yonesaka, Taroh Satoh, Yoshikazu Shimomura, Kazuhiko Nakagawa

JOURNAL OF CLINICAL ONCOLOGY　29　(23)　E678-E679　2011年8月

DOI： 10.1200/JCO.2011.35.0694 　

ISSN：0732-183X
[A review of FOLFOXIRI chemotherapy for the 1st line treatment of metastatic colorectal cancer]. 査読有り

Kawakami H, Satoh T, Nakagawa K

Nihon rinsho. Japanese journal of clinical medicine　69 Suppl 3　439-445　2011年4月
出版者・発行元：日本臨床社
ISSN：0047-1852
Paclitaxel療法後Docetaxel療法を行った進行再発胃癌14例の検討

工藤敏啓, 佐藤太郎, 川上尚人, 上田眞也, 宮崎昌樹, 藤阪保人, 鶴谷純司, 倉田宝保, 岡本勇, 中川和彦

日本胃癌学会総会記事　83回　188-188　2011年3月
出版者・発行元： (一社)日本胃癌学会
Seven cases of gemcitabine-induced lung injury during treatment for pancreatic or biliary tract cancers 査読有り

Takehiko Tsumura, Hiroo Matsuo, Takanori Maruo, Hisato Kawakami, Kiyoaki Hatano, Sumio Saito, Norihiro Nishijima, Masato Nakatsuji, Atsuyuki Ikeda, Hiroki Nishikawa, Ryuichi Kita, Yoshihiro Okabe, Toru Kimura, Ryoichi Amitani, Yukio Osaki

Japanese Journal of Cancer and Chemotherapy　36　(5)　785-788　2009年
出版者・発行元： Japanese Journal of Cancer and Chemotherapy Publishers Inc.
ISSN：0385-0684
コロナ様濃染を認めた限局性結節性過形成(FNH)の1症例査読有り

喜多竜一, 中辻正人, 西島規浩, 川上尚人, 波多野貴昭, 松尾裕央, 齋藤澄夫, 池田敦之, 那須章洋, 西川浩樹, 木村達, 大崎往夫, 中島収

日本消化器病學會雜誌 = The Japanese journal of gastro-enterology　105　(4)　550-557　2008年
出版者・発行元：一般財団法人日本消化器病学会
DOI： 10.11405/nisshoshi.105.550 　

ISSN：0446-6586
[Lemierre's syndrome with acute renal failure]. 査読有り

Iwamoto Y, Kawakami H, Kishi F, Miyamoto M, Minakata T

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine　96　(12)　2792-2793　2007年12月
出版者・発行元：一般社団法人日本内科学会
DOI： 10.2169/naika.96.2792 　

ISSN：0021-5384

詳細を見る詳細を閉じる

Lemierre症候群は口腔咽頭領域の感染に伴って生ずる内頸静脈の血栓性静脈炎と播種性感染性塞栓症を特徴とする．症例は31歳女性，近医から急性咽頭炎と腎不全とのことで当科を紹介受診となった．入院後の精査にて急性腎不全を合併したLemierre症候群と診断し，抗生物質にて加療した．腎不全に対しては血液透析を施行した．炎症反応の改善に伴い腎機能も改善し計8回の血液透析を施行した後離脱することができた．<br>

︎全件表示 ︎最初の5件までを表示

MISC 196

胃癌におけるCLDN18.2中等度発現の腫瘍内不均一性に関する研究(Intratumoral Heterogeneity of Intermediate CLDN18.2 Expression in Gastric Cancer)

川中雄介, 稲垣千晶, 大倉將生, 三谷誠一郎, 白石直樹, 坂井和子, 西尾和人, 木村豊, 千葉康敬, 若狭朋子, 川上尚人, 林秀敏

日本胃癌学会総会記事　98回　922-922　2026年3月
出版者・発行元： (一社)日本胃癌学会
DOI： 10.1007/s10147-026-03118-8 　

詳細を見る詳細を閉じる

BACKGROUND: CLDN18.2-targeted therapies show promise in HER2-negative, CLDN18.2-positive advanced gastric cancer (GC); however, cutoffs defining CLDN18.2 positivity vary across studies. Tumors with high expression (moderate to strong membranous expression in ≥ 75% of tumor cells) generally exhibit intratumoral homogeneity and a uniform staining pattern, but intratumoral heterogeneity and staining pattern of CLDN18.2 at lower expression thresholds remains unclear. This study investigated intratumoral heterogeneity of CLDN18.2 by comparing inter-block concordance of expression levels and staining patterns in GC. METHODS: Eighty-six resected GC specimens were retrospectively analyzed using CLDN18.2 immunohistochemistry on two tissue blocks per tumor. CLDN18.2 expression was categorized as high (≥ 75%), intermediate (< 75% and ≥ 40%), or negative (< 40%), and staining patterns as uniform or variable. Inter-block concordance of expression levels and staining patterns and their influence on concordance and outcomes were assessed. RESULTS: Overall inter-block concordance of expression levels was high (77%, κ = 0.89). Discordance was substantially higher in intermediate expression tumors (63.5%) than in high (15.5%) or negative (19%) expression tumors. Uniform staining was observed exclusively in high expression tumors, whereas all intermediate expression tumors displayed variable staining (100%). Among high expression tumors, inter-block concordance was substantially higher with uniform staining (98.0%) than with variable staining (71.5%). CLDN18.2 expression and staining pattern heterogeneity were not associated with worse survival. CONCLUSION: Significant intratumoral heterogeneity of CLDN18.2 expression was observed in GC, particularly in intermediate expression tumors; however, this heterogeneity does not affect survival. These results highlight the importance of standardized assessment methods when applying lower thresholds for CLDN18.2-targeted therapies.
包括的がんゲノムプロファイリング検査から遺伝性腫瘍と判明した家系血縁者の遺伝学的検査に関する後方視的検討

川村真亜子, 城田英和, 小峰啓吾, 高橋雅信, 川上尚人, 津幡真理, 新堀哲也, 青木洋子, 正宗淳

日本遺伝カウンセリング学会誌　46　(2)　110-110　2025年7月
出版者・発行元： (一社)日本遺伝カウンセリング学会
ISSN： 1347-9628
Chromosomal instability leads to EGFR-TKI refractoriness via cGAS-STING activation in EGFR-mutated non-small cell lung cancer

Kimio Yonesaka, Takashi Kurosaki, Junko Tanizaki, Hisato Kawakami, Kaoru Tanaka, Osamu Maenishi, Shiki Takamura, Kazuko Sakai, Yasutaka Chiba, Takeshi Teramura, Hiroki Goto, Eri Otsuka, Hiroaki Okida, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Yasuki Kamai, Takashi Kagari, Kazuto Nishio, Kazuhiro Kakimi, Hidetoshi Hayashi

CANCER RESEARCH　85　(8)　2025年4月15日

DOI： 10.1158/1538-7445.AM2025-424 　

ISSN： 0008-5472

eISSN： 1538-7445
HER2陽性切除不能進行・再発胃癌患者におけるトラスツズマブデルクステカン治療の予後因子:EN-DEAVOR研究サブ解析

杉本直俊, 中西香企, 小寺泰弘, 小寺泰弘, 川上尚人, 川上尚人, 牧山明資, 小西博貴, 森田智視, 成田有季哉, 三梨桂子, 今野元博, 稲本林, 仁科智裕, 川上武志, 萩原資久, 久米紘幹, 山口敬太, 橋本航, 室圭

日本臨床腫瘍学会学術集会(CD-ROM)　22nd　2025年
Impact of PD-L1 expression on survival in patients with unresectable/recurrent gastric cancer receiving first-line chemotherapy without immune checkpoint inhibitors.

Hidekazu Hirano, Yasuhide Yamada, Kengo Nagashima, Nobuyoshi Hiraoka, Shigeki Sekine, Naoki Takahashi, Mizutomo Azuma, Satoru Iwasa, Keisuke Kanato, Nozomu Machida, Takahiro Kinoshita, Hiroaki Hata, Hisato Kawakami, Daisuke Takahari, Toshiyasu Ojima, Shigenori Kadowaki, Narikazu Boku, Yukinori Kurokawa, Masanori Terashima, Takaki Yoshikawa

JOURNAL OF CLINICAL ONCOLOGY　42　(3_SUPPL)　391-391　2024年1月20日

DOI： 10.1200/JCO.2024.42.3_suppl.391 　

ISSN： 0732-183X

eISSN： 1527-7755
近畿大学病院免疫関連有害事象対策チームimNET活動の現状と課題

高濱隆幸, 磯本晃佑, 鈴木慎一郎, 渡邉諭美, 金村宙昌, 稲垣千晶, 三谷誠一郎, 谷崎潤子, 吉田健史, 田中薫, 川上尚人, 岩朝勤, 米阪仁雄, 藤原季美子, 萩原智, 西山理, 桑原基, 竹久志穂, 高橋直美, 林秀敏

日本臨床腫瘍学会学術集会(CD-ROM)　21st　2024年
Analysis of plasma angiogenesis factors on the efficacy of first-line (1L) chemotherapy (chemo) combined with biologics in RAS wild-type metastatic colorectal cancer (mCRC): Results from GI-SCREEN CRC Ukit study.

Satoshi Yuki, Yu Sunakawa, Kentaro Yamazaki, Hiromichi Shirasu, Hiroya Taniguchi, Toshiki Masuishi, Manabu Shiozawa, Hideaki Bando, Tomohiro Nishina, Hisateru Yasui, Takashi Ohta, Naoki Takahashi, Tadamichi Denda, Taito Esaki, Hisato Kawakami, Hironaga Satake, Atsuo Takashima, Yukiko Abe, Shogo Nomura, Takayuki Yoshino

JOURNAL OF CLINICAL ONCOLOGY　40　(16)　2022年6月

ISSN： 0732-183X

eISSN： 1527-7755
StageIII大腸癌における癌線維芽細胞MMP14の生物学意義の検討

幕谷悠介, 川上尚人, 家根由典, 牛嶋北斗, 吉岡康多, 和田聡朗, 岩本哲好, 大東弘治, 上田和毅, 所忠男, 川村純一郎

日本バイオセラピィ学会学術集会総会プログラム・抄録集　35th　2022年
BRCA2シングルサイト検査を同時に受検した姉妹の遺伝カウンセリング

大道納菜子, 川上尚人, 池川敦子, 池川敦子, 小田いつき, 奥田亜弥, 木下善仁, 田村和朗, 田村和朗, 西郷和真, 西郷和真

日本遺伝カウンセリング学会誌　43　(2)　2022年

ISSN： 1347-9628
MMP14発現が腫瘍免疫微小環境に与える影響

幕谷悠介, 川上尚人, 辻川敬裕, 家根由典, 牛嶋北斗, 原谷浩司, 吉岡康多, 和田聡明, 岩本哲好, 大東弘治, 上田和毅, 所忠男, 中川和彦, 川村純一郎

日本外科学会定期学術集会(Web)　122nd　2022年
EGFR inhibitor upregulates HER3 expression and enhances the efficacy of anti-HER3 antibody drug conjugate U3-1402

Kimio Yonesaka, Junko Tanizaki, Osamu Maenishi, Hisato Kawakami, Kaoru Tanaka, Hidetoshi Hayashi, Masayuki Takeda, Kazuko Sakai, Maki Kobayashi, Ryoto Yoshimoto, Hiroki Goto, Masanori Funabashi, Yuuri Hashimoto, Kenji Hirotani, Takashi Kagari, Kazuto Nishio, Kazuhiko Nakagawa

ANNALS OF ONCOLOGY　32　S296-S296　2021年7月

DOI： 10.1016/j.annonc.2021.05.567 　

ISSN： 0923-7534

eISSN： 1569-8041
【消化管がん】胃がん・大腸がんに対するADCの展開

黒崎隆, 川上尚人

腫瘍内科　27　(6)　648-654　2021年6月
出版者・発行元： (有)科学評論社
ISSN： 1881-6568
BRAF変異陽性大腸癌の新たな治療戦略

川上尚人, 緒方壮太

癌と化学療法　48　(6)　787-795　2021年6月
出版者・発行元： (株)癌と化学療法社
ISSN： 0385-0684
高用量CDDの使用が困難な進行食道癌患者に対する術前5-FU+docetaxel+nedaplatin(UDON)療法の治療成績

木村豊, 白石治, 加藤寛章, 百瀬洸太, 川上尚人, 平木洋子, 安田篤, 新海政幸, 今野元博, 安田卓司

日本外科学会定期学術集会抄録集　121回　SF-6　2021年4月
出版者・発行元： (一社)日本外科学会
【消化器領域のがん薬物療法-最近の動向-】切除不能進行再発大腸癌に対する薬物療法

黒崎隆, 川上尚人

消化器内科　3　(3)　21-32　2021年3月
出版者・発行元： (株)医学出版
日本胃癌学会「胃癌認定施設制度」について薬物療法の観点から

川上尚人, 山口研成, 藤原義之

日本胃癌学会総会記事　93回　148-148　2021年3月
出版者・発行元： (一社)日本胃癌学会
胃癌周術期薬物治療の挑戦 cSS/SE N1-3 M0胃癌に対する周術期capecitabine plus oxaliplatin(CapeOx)療法の第II相試験(A phase II study of perioperative CapeOx for clinical SS/SE N1-3 M0 gastric cancer(OGSG1601))

赤丸祐介, 松山仁, 寺澤哲司, 後藤昌弘, 川端良平, 遠藤俊治, 川上尚人, 黒川幸典, 下川敏雄, 坂井大介, 藤谷和正, 佐藤太郎

日本胃癌学会総会記事　93回　208-208　2021年3月
出版者・発行元： (一社)日本胃癌学会
進展胃癌に対する薬物治療はこれからどう変わるか? MSI-H進行胃癌に対する1次治療としてのニボルマブと低用量イピリムマブ併用の第II相試験(NO LIMIT試験)(Phase II study of Nivolumab plus Low dose Ipilimumab In gastric MSI-H Tumor(NO LIMIT))

川上尚人, 小松嘉人, 藪崎裕, 原浩樹, 平田賢郎, 平野秀和, 町田望, 牧山明資, 門脇重憲, 杉本直俊, 津田政広, 茶山一彰, 江崎泰斗, 廣中秀一, 室圭

日本胃癌学会総会記事　93回　210-210　2021年3月
出版者・発行元： (一社)日本胃癌学会
未治療切除不能進行・再発胃癌に対するマイクロサテライト不安定性を評価する観察研究(WJOG13320GPS)(An observational study of MSI screening in chemo-naive advanced gastric cancer: WJOG13320GPS)

小森梓, 廣中秀一, 川上尚人, 山崎健太郎, 室圭, WJOG13320GPS研究グループ

日本胃癌学会総会記事　93回　307-307　2021年3月
出版者・発行元： (一社)日本胃癌学会
【新型コロナウイルス関連特集】診療面(実践報告5) 各遺伝子医療部門の取り組み遺伝性神経疾患を多く扱っている施設コロナ下の近畿大学病院遺伝子診療部における状況

西郷和真, 池川敦子, 木戸滋子, 川上尚人, 武田真幸, 岩朝勤, 巽純子, 福岡和也, 西尾和人, 田村和朗, 中川和彦, 松村謙臣

日本遺伝カウンセリング学会誌　41　(4)　284-286　2021年2月
出版者・発行元： (一社)日本遺伝カウンセリング学会
ISSN： 1347-9628
大腸癌の腫瘍免疫微小環境におけるMMP14発現の影響

幕谷悠介, 川上尚人, 家根由典, 牛嶋北斗, 吉岡康多, 和田聡朗, 岩本哲好, 大東弘治, 上田和毅, 所忠男, 川村純一郎

日本バイオセラピィ学会学術集会総会プログラム・抄録集　34th　2021年
Expression of PD-L1 and PD-L2 in colorectal cancer (CRC): A post-hoc integrated analysis of SCRUM-Japan GI-SCREEN CRC.

Satoshi Yuki, Yoshiaki Nakamura, Hiroya Taniguchi, Tadamichi Denda, Tomohiro Nishina, Yasuo Hamamoto, Hiroki Hara, Taito Esaki, Hisato Kawakami, Atsuo Takashima, Taroh Satoh, Yu Sunakawa, Toshiki Masuishi, Eiji Shinozaki, Toshikazu Moriwaki, Izumi Miki, Kohei Shitara, Takayuki Yoshino

JOURNAL OF CLINICAL ONCOLOGY　39　(3)　2021年1月

DOI： 10.1200/JCO.2021.39.3_suppl.120 　

ISSN： 0732-183X

eISSN： 1527-7755
ベンダムスチン塩酸塩経口剤(SyB C-0501)の進行性固形がん患者に対する第1相臨床試験

武田真幸, 武田真幸, 中川和彦, 林秀敏, 岩朝勤, 川上尚人, 渡邉諭美, 山本昇, 米盛勧, 小山隆文, 佐藤潤, 田村研治, 菊池圭一, 赤池健一郎, 竹田志保, 清水俊雄

日本癌治療学会学術集会(Web)　59th　2021年
高用量CDDPの使用が困難な食道癌患者に対する3剤併用術前化学療法の検討

木村豊, 白石治, 川上尚人, 岩間密, 加藤寛章, 百瀬洸太, 安田篤, 新海政幸, 今野元博, 安田卓司

日本食道学会学術集会プログラム・抄録集　74回　349-349　2020年12月
出版者・発行元： (NPO)日本食道学会
消化器癌化学療法の進歩と課題 CDDPを使用できない食道癌患者に対する3剤併用術前化学療法の検討

木村豊, 白石治, 川上尚人, 安田卓司

日本消化器病学会近畿支部例会プログラム・抄録集　113回　51-51　2020年10月
出版者・発行元：日本消化器病学会-近畿支部
大腸癌化学療法の治療選択に有用なバイオマーカー HER2発現の転移性大腸癌患者を対象としたT-DXdの多施設共同第II相試験

舛石俊樹, Siena Salvatore, Di Bartolomeo Maria, Raghav Kanwal Pratap Singh, Loupakis Fotios, 川上尚人, 山口研成, 仁科智裕, Fakih Marwan, Elez Elena, Rodriguez Javier, Ciardiello Fortunato, 小林孝二郎, Grothey Axel, 吉野孝之

日本癌治療学会学術集会抄録集　58回　WS6-1　2020年10月
出版者・発行元： (一社)日本癌治療学会
胃癌化学療法の治療選択に有用なバイオマーカー HER2陽性の進行胃腺癌患者を対象としたT-DXdの多施設共同第II相試験

杉本直俊, 設樂紘平, Bang Yung-Jue, 岩佐悟, Ryu Min-Hee, 坂井大介, Chung Hyun Cheol, 川上尚人, 藪崎裕, Lee Jeeyun, 山口研成

日本癌治療学会学術集会抄録集　58回　WS17-1　2020年10月
出版者・発行元： (一社)日本癌治療学会
多剤併用療法が適さないRAS野生型大腸がんに対する一次治療パニツムマブ単剤療法

佐竹悠良, 加藤健志, 後藤昌弘, 寺澤哲志, 太田勝也, 能浦真吾, 賀川義規, 川上尚人, 長谷川裕子, 坂井大介, 黒川幸典, 下川敏雄, 佐藤太郎

日本癌治療学会学術集会抄録集　58回　O26-1　2020年10月
出版者・発行元： (一社)日本癌治療学会
【臓器別やさしい消化器がん化学療法・薬物療法 32のレジメン×副作用ケア×退院指導】(Chapter 3)消化器がんの病態と治療大腸がん

黒崎隆, 川上尚人

消化器ナーシング　(2020秋季増刊)　73-81　2020年10月
出版者・発行元： (株)メディカ出版
ISSN： 2434-4575
HER2陰性再発・進行胃癌に対するSP療法とXP療法との比較 HERBIS-2(OGSG 1103)とHERBIS-4A(OGSG 1105)試験との統合解析

赤丸祐介, 川上尚人, 藤谷和正, 松山仁, 後藤昌弘, 田村茂行, 遠藤俊治, 木村豊, 辻仲利政, 間狩洋一, 田村孝雄, 杉本直俊, 坂井大介, 黒川幸典, 下川敏雄, 佐藤太郎

日本外科学会定期学術集会抄録集　120回　SF-2　2020年8月
出版者・発行元： (一社)日本外科学会
頭頸部癌における免疫チェックポイント阻害薬後のセツキシマブ使用の有効性および安全性

三谷誠一郎, 田中薫, 鈴木慎一郎, 原谷浩司, 文田壮一, 川上尚人, 吉田健史, 林秀敏, 北野睦三, 土井勝美, 石川一樹, 西村恭昌, 中川和彦

頭頸部癌　46　(2)　218-218　2020年7月
出版者・発行元： (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
消化器癌に対する免疫療法の現状と展望切除不能進行・再発胃癌に対するニボルマブ単剤療法の臨床的効果予測因子の検討

黒崎隆, 川上尚人, 中川和彦

日本消化器病学会雑誌　117　(臨増総会)　A26-A26　2020年7月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
切除不能進行・再発胃がん後方ライン治療への切り替えタイミングとポイント

川上尚人

胃がんperspective　11　(2)　172-177　2020年7月
出版者・発行元： (株)メディカルレビュー社
ISSN： 1883-3330
【検査値を読む2020】(30章)腫瘍関連検査糖鎖抗原19-9(CA19-9)

文田壮一, 川上尚人

内科　125　(4)　1073-1073　2020年4月
出版者・発行元： (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
【検査値を読む2020】(30章)腫瘍関連検査糖鎖抗原50(CA50)

文田壮一, 川上尚人

内科　125　(4)　1074-1074　2020年4月
出版者・発行元： (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
【検査値を読む2020】(30章)腫瘍関連検査 SPan-1

文田壮一, 川上尚人

内科　125　(4)　1075-1075　2020年4月
出版者・発行元： (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
【検査値を読む2020】(30章)腫瘍関連検査 DUPAN-2

文田壮一, 川上尚人

内科　125　(4)　1076-1076　2020年4月
出版者・発行元： (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
【検査値を読む2020】(30章)腫瘍関連検査 NCC-ST-439

文田壮一, 川上尚人

内科　125　(4)　1077-1077　2020年4月
出版者・発行元： (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
【検査値を読む2020】(30章)腫瘍関連検査尿中遊離型フコース(UFC)

文田壮一, 川上尚人

内科　125　(4)　1078-1078　2020年4月
出版者・発行元： (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
非小細胞肺癌患者における免疫チェックポイント阻害薬による消化管irAEにおけるヒト・腸内細菌叢の病態と炎症性腸疾患の類似性に関する検討

西尾和人, 坂井和子, 櫻井俊治, 上嶋一臣, 永井知行, 林秀敏, 川上尚人, 高濱隆幸, 武田真幸, 中川和彦

肺癌　60　(2)　165-165　2020年4月
出版者・発行元： (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
【消化器領域における免疫チェックポイント阻害薬の現状・今後の展望】免疫チェックポイント阻害薬と他剤との併用療法

三谷誠一郎, 川上尚人, 中川和彦

臨床消化器内科　35　(5)　495-500　2020年4月
出版者・発行元： (株)日本メディカルセンター
ISSN： 0911-601X

eISSN： 2433-2488
A phase II trial of low-dose nab-paclitaxel for patients with previously treated or recurrent advanced gastric cancer (OGSG1302)

Masashi Hirota, Shigeyuki Tamura, Hirokazu Taniguchi, Atsushi Takeno, Hiroshi Imamura, Junya Fujita, Jin Matsuyama, Yutaka Kimura, Junji Kawada, Motohiro Hirao, Kazuhiro Nishikawa, Kazumasa Fujitani, Yukinori Kurokawa, Daisuke Sakai, Hisato Kawakami, Toshio Shimokawa, Taroh Satoh

JOURNAL OF CLINICAL ONCOLOGY　38　(4)　2020年2月

ISSN： 0732-183X

eISSN： 1527-7755
Comparing five-weekly S-1 plus cisplatin with tri-weekly capecitabine plus cisplatin in patients with HER2-negative recurrent gastric cancer after S-1 adjuvant therapy or chemotherapy naive advanced gastric cancer: A pooled analysis of HERBIS-2 (OGSG 1103) and HERBIS-4A (OGSG 1105) trials

Jin Matsuyama, Hisato Kawakami, Kazumasa Fujitani, Yusuke Akamaru, Shigeyuki Tamura, Shunji Endo, Yutaka Kimura, Youichi Makari, Takao Tamura, Naotoshi Sugimoto, Daisuke Sakai, Toshimasa Tsujinaka, Masahiro Goto, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

JOURNAL OF CLINICAL ONCOLOGY　38　(4)　2020年2月

ISSN： 0732-183X

eISSN： 1527-7755
Phase II study of panitumumab monotherapy in chemotherapy-naive frail or elderly patients with unresectable, RAS wild-type colorectal cancer: OGSG 1602

Katsuya Ohta, Takeshi Kato, Masahiro Goto, Tetsuji Terazawa, Shingo Noura, Hironaga Satake, Yoshinori Kagawa, Hisato Kawakami, Hiroko Hasegawa, Kazuhiro Yanagihara, Tatsushi Shingai, Ken Nakata, Masahito Kotaka, Masayuki Hiraki, Ken Konishi, Shiro Nakae, Daisuke Sakai, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh

JOURNAL OF CLINICAL ONCOLOGY　38　(4)　2020年2月

ISSN： 0732-183X

eISSN： 1527-7755
消化器がん薬物療法up to date 切除不能進行再発胃癌に対するニボルマブ単独療法の臨床的予後予測因子の検討

黒崎隆, 川上尚人, 三谷誠一郎, 中川和彦

日本消化器病学会近畿支部例会プログラム・抄録集　112回　71-71　2020年2月
出版者・発行元：日本消化器病学会-近畿支部
Pulmonary tumor thrombotic microangiopathy(PTTM)により急激な転機をたどった下咽頭癌患者の一例

川中雄介, 川上尚人, 中川和彦, 吉田健史, 清水重喜

日本内科学会雑誌　109　(Suppl.)　231-231　2020年2月
出版者・発行元： (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
irAE大腸炎を契機にICIの関与が疑われたStevens-Johnson症候群の1例

黒崎隆, 川上尚人, 文田壮一, 三谷誠一郎, 中川和彦

日本内科学会雑誌　109　(Suppl.)　260-260　2020年2月
出版者・発行元： (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
非小細胞肺癌患者における免疫チェックポイント阻害薬による消化管irAEにおけるヒト・腸内細菌叢の病態と炎症性腸疾患の類似性に関する検討

西尾和人, 坂井和子, 櫻井俊治, 上嶋一臣, 永井知行, 林秀敏, 川上尚人, 高濱隆幸, 武田真幸, 中川和彦

肺癌(Web)　60　(2)　2020年

ISSN： 1348-9992
腎機能低下を伴う進行食道癌患者に対する安全な3剤併用術前化学療法(UDON療法)

木村豊, 白石治, 岩間密, 加藤寛章, 川上尚人, 奥野達哉, 平木洋子, 安田篤, 新海政幸, 今野元博, 中川和彦, 安田卓司

癌と化学療法　46　(13)　2173-2175　2019年12月
出版者・発行元： (株)癌と化学療法社
ISSN： 0385-0684
【新しい抗体薬;ADC】消化器がんに対するADC

佐藤千尋, 三谷誠一郎, 川上尚人

がん分子標的治療　17　(2)　133-138　2019年12月
出版者・発行元： (株)メディカルレビュー社
ISSN： 1347-6955
高齢の進行食道癌患者に対する3剤併用術前化学療法の有用性とその課題

木村豊, 白石治, 岩間密, 加藤寛章, 川上尚人, 平木洋子, 安田篤, 新海政幸, 今野元博, 中川和彦, 安田卓司

日本消化器病学会雑誌　116　(臨増大会)　A832-A832　2019年11月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
高齢の進行食道癌患者に対する3剤併用術前化学療法の有用性とその課題

木村豊, 白石治, 岩間密, 加藤寛章, 川上尚人, 平木洋子, 安田篤, 新海政幸, 今野元博, 中川和彦, 安田卓司

日本消化器病学会雑誌　116　(臨増大会)　A832-A832　2019年11月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
新規臨床試験最新情報食道がんに対するニボルマブの開発状況について

高橋雅信, 加藤健, 岡田守人, 陳勁松, 門脇重憲, 浜本康夫, 土岐祐一郎, 久保田祐太郎, 川上尚人, 尾形高士, 原浩樹, 武藤学, 中島雄一郎, 北川雄光

日本癌治療学会学術集会抄録集　57回　SSY14-4　2019年10月
出版者・発行元： (一社)日本癌治療学会
新規臨床試験最新情報根治切除可能な4型・大型3型胃癌に対する術前化学放射線療法第II相試験(OGSG1205)

李相雄, 今野元博, 古河洋, 横川正樹, 西村恭昌, 安田卓司, 遠藤俊治, 後藤昌弘, 紀貴之, 内山和久, 川上尚人, 下川敏雄, 坂井大介, 黒川幸典, 佐藤太郎, 大阪消化管がん化学療法研究会(OGSG)

日本癌治療学会学術集会抄録集　57回　SSY14-5　2019年10月
出版者・発行元： (一社)日本癌治療学会
転移性肝癌国際診療ガイドライン薬物治療

中島貴子, 水上拓郎, 武田弘幸, 川上尚人, 奥野尚弘, 上野誠, 肱岡範, 尾阪将人, 上野貴之, 内藤陽一, 古瀬純司

日本癌治療学会学術集会抄録集　57回　JHPBS-6　2019年10月
出版者・発行元： (一社)日本癌治療学会
75歳以上の根治切除可能な大型3型/4型胃癌に対する術前S-1併用化学放射線療法OGSG1303

遠藤俊治, 今野元博, 古河洋, 安田卓司, 横川正樹, 西村恭昌, 中川朋, 足立真一, 木村豊, 坂井大介, 川上尚人, 下川敏雄, 黒川幸典, 佐藤太郎

日本癌治療学会学術集会抄録集　57回　P71-1　2019年10月
出版者・発行元： (一社)日本癌治療学会
こんなにある薬剤性消化管傷害[各論小腸および大腸]免疫チェックポイント阻害薬による大腸病変

櫻井俊治, 樫田博史, 永井知行, 米田頼晃, 川上尚人, 中川和彦, 工藤正俊

消化器内視鏡　31　(6)　928‐933-933　2019年6月25日
出版者・発行元： (株)東京医学社
ISSN： 0915-3217
悪性リンパ腫放射線治療後、2次発癌として進行食道癌を併発した1例

奥野達哉, 武川直樹, 野長瀬祥兼, 川上尚人, 林秀敏, 中川和彦

日本食道学会学術集会プログラム・抄録集　73回　258-258　2019年6月
出版者・発行元： (NPO)日本食道学会
A dose-finding study for irinotecan, cisplatin, and S-1 (IPS) in patients with advanced gastric cancer (OGSG 1106).

Hiroki Yukami, Masahiro Goto, Takayuki Kii, Tetsuji Terazawa, Toshifumi Yamaguchi, Fukutaro Shimamoto, Hitoshi Nishitani, Hisato Kawakami, Toshio Shimokawa, Yoshihiro Matsubara, Daisuke Sakai, Yukinori Kurokawa, Taroh Satoh

JOURNAL OF CLINICAL ONCOLOGY　37　(4)　2019年2月

DOI： 10.1200/JCO.2019.37.4_suppl.144 　

ISSN： 0732-183X

eISSN： 1527-7755
【大腸がん薬物療法-実臨床で必要な最新知識】大腸がんに対する免疫療法は有効か? 今後の展望

渡邉諭美, 川上尚人

臨床腫瘍プラクティス　15　(1)　45-50　2019年2月
出版者・発行元： (株)ヴァンメディカル
ISSN： 1880-3083
REVIVE study: Prospective observational study of efficacy and safety in chemotherapy (CTx) after progressive disease of nivolumab (NIV) therapy for metastatic gastric cancer (mGC).

Yukiya Narita, Hirokazu Shoji, Sadayuki Kawai, Takuro Mizukami, Michio Nakamura, Toshikazu Moriwaki, Takeharu Yamanaka, Yu Sunakawa, Hisato Kawakami, Tomohiro Nishina, Toshihiro Misumi, Yu Yamashige, Akira Yamashige, Kei Muro

JOURNAL OF CLINICAL ONCOLOGY　37　(4)　2019年2月

DOI： 10.1200/JCO.2019.37.4_suppl.TPS178 　

ISSN： 0732-183X

eISSN： 1527-7755
高齢の進行食道癌患者に対する3剤併用術前化学療法の開発

木村豊, 白石治, 岩間密, 加藤寛章, 川上尚人, 安田篤, 新海政幸, 今野元博, 中川和彦, 安田卓司

日本食道学会学術集会抄録集(CD-ROM)　73rd　328-328　2019年
出版者・発行元： (NPO)日本食道学会
高用量CDDPの使用が困難な進行食道癌患者に対する術前化学療法の検討

木村豊, 白石治, 川上尚人, 植田勲人, 奥野達哉, 岩間密, 加藤寛章, 平木洋子, 安田篤, 新海政幸, 今野元博, 今本治彦, 中川和彦, 安田卓司

日本消化器外科学会雑誌　51　(Suppl.2)　268-268　2018年11月
出版者・発行元： (一社)日本消化器外科学会
ISSN： 0386-9768

eISSN： 1348-9372
当院でのirAE大腸炎の臨床的特徴

櫻井俊治, 川上尚人, 工藤正俊

日本消化器病学会雑誌　115　(臨増大会)　A441-A441　2018年10月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
【消化管がん】希少フラクションを標的とした切除不能・進行再発大腸がんの臨床開発

川上尚人

腫瘍内科　22　(1)　17-23　2018年7月
出版者・発行元： (有)科学評論社
ISSN： 1881-6568
悪性リンパ腫放射線治療後、2次発癌として進行食道癌を併発した1例

奥野達哉, 植田勲人, 武川直樹, 野長瀬祥兼, 川上尚人, 谷崎潤子, 林秀敏, 田中薫, 武田真幸, 鶴谷純司, 中川和彦

日本消化器病学会雑誌　115　(臨増総会)　A328-A328　2018年4月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586
悪性リンパ腫放射線治療後、2次発癌として進行食道癌を併発した1例

奥野達哉, 植田勲人, 武川直樹, 野長瀬祥兼, 川上尚人, 谷崎潤子, 林秀敏, 田中薫, 武田真幸, 鶴谷純司, 中川和彦

日本消化器病学会雑誌　115　(臨増総会)　A328-A328　2018年3月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
The nationwide screening project on plasma angiogenesis-related mediators for treatment selection of optimal antiangiogenic inhibitors in metastatic colorectal cancer: GI-SCREEN CRC-Ukit.

Satoshi Yuki, Kentaro Yamazaki, Hiroya Taniguchi, Yu Sunakawa, Akihito Kawazoe, Yoshinori Kagawa, Ken Kato, Hiroki Hara, Tadamichi Denda, Eiji Oki, Toshikazu Moriwaki, Manabu Shiozawa, Taroh Satoh, HIsato Kawakami, Taito Esaki, Junji Furuse, Yukiko Abe, Shogo Nomura, Atsushi Ohtsu, Takayuki Yoshino

JOURNAL OF CLINICAL ONCOLOGY　36　(4)　2018年2月

DOI： 10.1200/JCO.2018.36.4_suppl.TPS885 　

ISSN： 0732-183X

eISSN： 1527-7755
Plasma ICAM-1 (pICAM-1) and plasma IL-8 (pIL-8) level as biomarker of metastatic colorectal cancer patients (mCRC) treated with mFOLFOX6/XELOX plus bevacizumab (BV) (WJOG7612GTR).

Yoshiyuki Yamamoto, Wataru Okamoto, Akitaka Makiyama, Kohei Shitara, Tadamichi Denda, Takashi Ogura, Yasuyuki Nakano, Tomohiro Nishina, Masato Komoda, Hiroki Hara, Yukinori Ozaki, HIsato Kawakami, Narikazu Boku, Ichinosuke Hyodo, Kentaro Yamazaki, Shuichi Hironaka, Kazuko Sakai, Takeharu Yamanaka, Kei Muro, Kazuto Nishio

JOURNAL OF CLINICAL ONCOLOGY　36　(4)　2018年2月

DOI： 10.1200/JCO.2018.36.4_suppl.670 　

ISSN： 0732-183X

eISSN： 1527-7755
Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naive patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial

Atsushi Takeno, Youichi Makari, Shunji Endo, Jin Matsuyama, Ryohei Kawabata, Naotoshi Sugimoto, Hirokazu Taniguchi, Kenichi Nagai, Shigeyuki Tamura, Junichi Nishijima, Shugo Ueda, Yutaka Kimura, Takao Tamura, Kenji Kobayashi, HIsato Kawakami, Kazumasa Fujitani, Daisuke Sakai, Toshio Shimokawa, Yukinori Kurokawa, Taroh Satoh

JOURNAL OF CLINICAL ONCOLOGY　36　(4)　2018年2月

DOI： 10.1200/JCO.2018.36.4_suppl.102 　

ISSN： 0732-183X

eISSN： 1527-7755
【免疫チェックポイント阻害薬によるがん治療】免疫チェックポイント阻害薬と個別化医療

武川直樹, 川上尚人

臨床腫瘍プラクティス　14　(1)　21-26　2018年2月
出版者・発行元： (株)ヴァンメディカル
ISSN： 1880-3083
治療抵抗性であった免疫関連性大腸炎に対して人工肛門造設術が有効であった1例

大東弘治, 上田和毅, 川村純一郎, 牛嶋北斗, 家根由典, 吉岡康多, 所忠男, 肥田仁一, 川上尚人, 奥野清隆

日本大腸肛門病学会雑誌(Web)　71　(9)　2018年

ISSN： 1882-9619
高齢の進行食道癌患者に対する3剤併用術前化学療法の検討

木村豊, 白石治, 川上尚人, 植田勲人, 加藤寛章, 岩間密, 安田篤, 新海政幸, 中川和彦, 安田卓司

日本食道学会学術集会抄録集(CD-ROM)　72nd　337-337　2018年
出版者・発行元： (NPO)日本食道学会
腎機能低下を伴う進行食道癌患者に対する安全な3剤併用術前化学療法(UDON療法)

木村豊, 白石治, 川上尚人, 奥野達哉, 岩間密, 加藤寛章, 平木洋子, 安田篤, 新海政幸, 今野元博, 中川和彦, 安田卓司

日本癌治療学会学術集会(Web)　56th　(13)　ROMBUNNO.P72‐5 (WEB ONLY)-2175　2018年
出版者・発行元： (株)癌と化学療法社
ISSN： 0385-0684
5-FU+docetaxel+nedaplatin併用術前化学療法が奏効した進行食道癌患者の1例

木村豊, 白石治, 川上尚人, 植田勲人, 奥野達哉, 平木洋子, 加藤寛章, 岩間密, 安田篤, 新海政幸, 筑後孝章, 今野元博, 今本治彦, 中川和彦, 安田卓司

癌と化学療法　45　(13)　1812-1814　2018年
出版者・発行元： (株)癌と化学療法社
ISSN： 0385-0684
〈第76回近畿大学医学会学術講演会〉heregulin 発現HER2陽性乳癌・胃癌における抗HER2薬ラパチニブ，トラスツズマブ，T-DM1の感受性に関する研究

野長瀬祥兼, 米阪仁雄, 川上尚人, 渡邉諭美, 原谷浩司, 高濱隆幸, 武川直樹, 植田勲人, 谷崎潤子, 林秀俊, 吉田健史, 武田真幸, 千葉康敬, 中川和彦, 鶴谷純司

近畿大学医学雑誌 = Medical Journal of Kindai University　42　(3)　25A1-25A1　2017年12月20日
出版者・発行元：近畿大学医学会
ISSN： 0385-8367
分子標的薬への耐性機構の解明 T790M陽性肺癌細胞株における第三世代EGFR-TKIとSrc阻害薬ダサチニブの併用効果の検討

吉田健史, 渡邉諭美, 武川直樹, 川上尚人, 中川和彦

肺癌　57　(5)　377-377　2017年9月
出版者・発行元： (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
【切除不能・進行再発大腸がん薬物治療-そのレジメン選択は正解か?】適切な個別化治療のために必要な最新知見抗VEGF抗体薬を使うべき症例、ひとまず様子を見るべき症例効果予測の観点から

川上尚人

臨床腫瘍プラクティス　13　(3)　177-180　2017年8月
出版者・発行元： (株)ヴァンメディカル
ISSN： 1880-3083
皮膚筋炎合併の胸腺癌患者に対する全人的苦痛の緩和に務めた1例

河野恵, 岩朝勤, 中西良子, 森田さやか, 徳留由貴, 川上尚人, 吉田健史, 三瀬博之, 宮崎巳美, 尾崎公俊

肺癌　57　(3)　250-251　2017年6月
出版者・発行元： (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
セツキシマブ耐性の大腸癌患者における血漿におけるHER2遺伝子増幅の検出

武川直樹, 米阪仁雄, 坂井和子, 野長瀬祥兼, 植田勲人, 奥野達哉, 前西修, 川上尚人, 鶴谷純司, 田村孝雄, 中川和彦

日本消化器病学会雑誌　114　(臨増総会)　A297-A297　2017年3月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
セツキシマブ耐性の大腸癌患者における血漿におけるHER2遺伝子増幅の検出

武川直樹, 米阪仁雄, 坂井和子, 野長瀬祥兼, 植田勲人, 奥野達哉, 前西修, 川上尚人, 鶴谷純司, 田村孝雄, 中川和彦

日本消化器病学会雑誌　114　(臨増総会)　A297-A297　2017年3月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586
MEK/ERK and MCL-1 inhibition synergistically reverse apoptosis resistance in colon cancer cells with BRAF(V600E)-mediated MCL-1 upregulation

Hisato Kawakami, Shengbing Huang, Frank A. Sinicrope

CANCER RESEARCH　76　2016年7月

DOI： 10.1158/1538-7445.AM2016-2115 　

ISSN： 0008-5472

eISSN： 1538-7445
Heregulin-induced resistance against HER2-targeted therapies in HER2 positive breast and gastric cancer in vitro and in vivo

Yoshikane Nonagase, Kimio Yonesaka, Satomi Watanabe, Koji Haratani, Takayuki Takahama, Naoki Takegawa, Hiroto Ueda, Hisato Kawakami, Hidetoshi Hayashi, Masayuki Takeda, Haruka Sakamoto, Takao Tamura, Kazuhiko Nakagawa, Junji Tsurutani

CANCER RESEARCH　76　2016年7月

DOI： 10.1158/1538-7445.AM2016-2939 　

ISSN： 0008-5472

eISSN： 1538-7445
Mutant BRAF (V600E) Phosphorylates MCL-1 to Increase Stability/Expression That Confers Apoptosis Resistance in Colorectal Cancer Cells

Hisato Kawakami, Shengbing Huang, Frank A. Sinicrope

GASTROENTEROLOGY　150　(4)　S372-S372　2016年4月

DOI： 10.1016/s0016-5085(16)31308-7 　

ISSN： 0016-5085

eISSN： 1528-0012
中咽頭癌に対する強度変調放射線治療(IMRT)の治療成績

建部仁志, 石川一樹, 横川正樹, 稲田正浩, 福田浩平, 松浦知弘, 立花和泉, 中松清志, 門前一, 金森修一, 西村恭昌, 川上尚人

Japanese Journal of Radiology　34　(Supplement)　54-54　2016年2月25日
出版者・発行元： (公社)日本医学放射線学会
ISSN： 1867-1071

eISSN： 1867-108X
中咽頭癌に対する強度変調放射線治療(IMRT)の治療成績

建部仁志, 石川一樹, 横川正樹, 稲田正浩, 福田浩平, 松浦知弘, 立花和泉, 中松清志, 門前一, 金森修一, 西村恭昌, 川上尚人

Japanese Journal of Radiology　34　(Suppl.)　54-54　2016年2月
出版者・発行元： (公社)日本医学放射線学会
ISSN： 1867-1071
HER2陽性乳癌・胃癌における抗HER2薬に対するHeregulinによる薬剤耐性に関する研究

野長瀬祥兼, 米阪仁雄, 渡邉諭美, 武川直樹, 川上尚人, 林秀敏, 武田真幸, 田村孝雄, 中川和彦, 鶴谷純司

日本臨床腫瘍学会学術集会(CD-ROM)　14th　2016年
Clinical significance of concurrent chemoradiotherapy for advanced esophageal cancer

UEDA Hiroto, TAKEDA Masayuki, UEDA Shinya, KAWAKAMI Hisato, TAKEGAWA Naoki, TAMURA Takao, ISHIKAWA Kazuki, NISHIMURA Yasumasa, NAKAGAWA Kazuhiko

日本臨床腫瘍学会学術集会(CD-ROM)　14th　ROMBUNNO.P2‐033　2016年
MEK/ERK inhibitor GDC-0623 dephosphorylates and accumulates BIM that enables a synergistic apoptosis with the Bcl-xL antagonist, ABT-263, in mutant KRAS colorectal cancer cells

Aziz Zaanan, Koichi Okamoto, Hisato Kawakami, Shengbing Huang, Frank Sinicrope

CANCER RESEARCH　75　2015年8月

DOI： 10.1158/1538-7445.AM2015-2937 　

ISSN： 0008-5472

eISSN： 1538-7445
Reversal of Mutant KRAS-Mediated Apoptosis Resistance by Concurrent Bcl-xL Antagonism and Induction of Pro-Apoptotic BH3-Only Proteins in Colorectal Carcinoma Cells

Koichi Okamoto, Hisato Kawakami, Shengbing Huang, Frank A. Sinicrope

GASTROENTEROLOGY　148　(4)　S15-S15　2015年4月

DOI： 10.1016/s0016-5085(15)30049-4 　

ISSN： 0016-5085

eISSN： 1528-0012
肺がん患者に対するマグネシウム補充によるシスプラチン関連腎障害の抑制効果の検討

木寺康裕, 川上尚人, 金田裕靖, 藤原季美子, 野村守弘, 千葉康敬, 西田升三, 山添譲, 鶴谷純司, 田村孝雄, 中川和彦

日本肺癌学会総会号　55th　(5)　409-409　2014年10月5日
出版者・発行元： (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
日本人進行固形がん患者に対するMK‐3475(抗PD‐1抗体)の第I相試験

清水俊雄, 瀬戸貴司, 平井文彦, 竹中朋祐, 鶴谷純司, 金田裕靖, 岩朝勤, 川上尚人, 野口一夫, 嶋本隆司, 中川和彦

日本肺癌学会総会号　55th　(5)　352-352　2014年10月5日
出版者・発行元： (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
HEREGULIN AS A BIOMARKER FOR ANTI-HER3 ANTIBODY PATRITUMAB COMBINED WITH ERLOTINIB IN NON-SMALL CELL LUNG CANCER

Kimio Yonesaka, Hisato Kawakami, Hiroyasu Kaneda, Isamu Okamoto, Kenji Hirotani, Kazuto Nishio, Kazuhiko Nakagawa

ANNALS OF ONCOLOGY　25　2014年10月

DOI： 10.1093/annonc/mdu435.123 　

ISSN： 0923-7534

eISSN： 1569-8041
Novel HER3 neutralizing antibody, patritumab abrogates cetuximab resistance mediated by a heregulin-autocrine loop in colorectal cancer

Hisato Kawakami, Isamu Okamoto, Kimio Yonesaka, Kunio Okamoto, Kiyoko Kuwata, Yume Morita, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa

CANCER RESEARCH　74　(19)　2014年10月

DOI： 10.1158/1538-7445.AM2014-1844 　

ISSN： 0008-5472

eISSN： 1538-7445
The expression level of HER3 ligand heregulin in mRNA as a predictive biomarker for anti-HER3 antibody patritumab combined with erlotinib in non-small cell lung cancer.

Kimio Yonesaka, Hisato Kawakami, Hiroyasu Kaneda, Isamu Okamoto, Kenji Hirotani, Kazuto Nishio, Kazuhiko Nakagawa

JOURNAL OF CLINICAL ONCOLOGY　32　(15)　2014年5月

DOI： 10.1200/jco.2014.32.15_suppl.e19082 　

ISSN： 0732-183X

eISSN： 1527-7755
進行再発食道癌に対するドセタキセル,ネダプラチン,5‐FUによる第一相試験

仁科慎一, 上田眞也, 野長瀬祥兼, 岡部崇記, 崎山努, 川上尚人, 田村孝雄, 中川和彦

日本臨床腫瘍学会学術集会(CD-ROM)　12th　ROMBUNNO.P2-5-4　2014年
膵癌,大腸癌の重複癌に対してSOX‐Bevacizumabが奏効した1例

高濱隆幸, 野長瀬祥兼, 崎山勉, 川上尚人, 仁科慎一, 田村孝雄, 中川和彦

日本臨床腫瘍学会学術集会(CD-ROM)　12th　ROMBUNNO.P2-12-6　2014年
分子標的としてのc‐METの可能性

川上尚人

日本胃癌学会総会記事　86th　135　2014年
肝機能障害を呈する胃癌肝転移患者に対しカペシタビンとシスプラチン併用療法が安全かつ効果的に投与できた一例

野長瀬祥兼, 崎山勉, 高濱隆幸, 川上尚人, 仁科慎一, 田村孝雄, 中川和彦

日本臨床腫瘍学会学術集会(CD-ROM)　12th　ROMBUNNO.P1-30-2　2014年
PHASE I PHARMACOKINETIC STUDY OF S-1 GRANULE AND NEDAPLATIN FOR PATIENTS WITH RECURRENT/METASTATIC HEAD AND NECK CANCER

K. Tanaka, H. Hayashi, I. Okamoto, S. Ueda, K. Okamoto, H. Kawakami, S. Nishina, M. Takeda, K. Doi, K. Nakagawa

ANNALS OF ONCOLOGY　24　2013年11月

DOI： 10.1093/annonc/mdt459.42 　

ISSN： 0923-7534

eISSN： 1569-8041
研修医からの質問Q&A 十二指腸乳頭部がん再発と原発性非小細胞肺癌の重複癌症例に対する治療の進め方は?

川上尚人, 亀井敬子

臨床腫瘍プラクティス　9　(3)　338-339　2013年8月
出版者・発行元： (株)ヴァンメディカル
ISSN： 1880-3083
いつごろ生じる?看護はどうする?がひとめでわかるがん化学療法の副作用速習おぼえ書き 5 味覚障害

川上尚人

プロフェッショナルがんナーシング　3　(3)　234-235　2013年6月1日

ISSN： 2185-7318
いつごろ生じる?看護はどうする?がひとめでわかるがん化学療法の副作用速習おぼえ書き 4 口内炎(口腔粘膜炎)

川上尚人

プロフェッショナルがんナーシング　3　(3)　232-233　2013年6月1日

ISSN： 2185-7318
MET amplification as a potential therapeutic target in gastric cancer.

Hisato Kawakami, Isamu Okamoto, Tokuzo Arao, Wataru Okamoto, Kazuko Matsumoto, Hirokazu Taniguchi, Kiyoko Kuwata, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa, Yasuhide Yamada

CANCER RESEARCH　73　(8)　4657-4657　2013年4月

DOI： 10.1158/1538-7445.AM2013-4657 　

ISSN： 0008-5472

eISSN： 1538-7445
EML4‐ALK陽性進行非小細胞肺癌における,初回白金併用化学療法の治療効果の検討

武田真幸, 岡本勇, 坂井和子, 川上尚人, 西尾和人, 中川和彦

日本内科学会雑誌　102　(Suppl.)　198-198　2013年2月20日
出版者・発行元： (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
切除不能胆道癌に対するCDDP+GEM療法

川上尚人, 岡本勇, 上田眞也, 岡本渉, 仁科慎一, 鶴谷純司, 倉田宝保, 中川和彦

日本内科学会雑誌　102　(Suppl.)　200-200　2013年2月20日
出版者・発行元： (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
進行再発食道癌に対するネダプラチンを用いた化学療法

仁科慎一, 上田眞也, 岡本渉, 川上尚人, 崎山勉, 岡本邦男, 金田裕靖, 田中薫, 吉田健史, 中川和彦

日本内科学会雑誌　102　199　2013年2月20日

ISSN： 0021-5384
腫瘍内科医が受けるストレス度,満足度についての当科でのアンケート調査

野長瀬祥兼, 崎山勉, 川上尚人, 松岡弘道, 田村孝雄, 小山敦子, 中川和彦

日本サイコオンコロジー学会総会プログラム・抄録集　26th　137　2013年
EGFR,HER2及びHER3阻害剤AZD8931の第1相試験―進行固形癌患者対象の単独投与及び進行再発乳癌患者対象のパクリタキセル併用―

鶴谷純司, 倉田宝保, 藤阪保仁, 岡本渉, 林秀敏, 川上尚人, 辛栄成, 林暢哉, 中川和彦

日本臨床腫瘍学会学術集会(CD-ROM)　11th　ROMBUNNO.P2-087　2013年
EML4‐ALK陽性進行非小細胞肺癌における,初回白金併用化学療法の治療効果の検討

武田真幸, 岡本勇, 坂井和子, 川上尚人, 西尾和人, 中川和彦

肺癌　52　(5)　510　2012年10月5日

ISSN： 0386-9628
ANTITUMOR ACTION OF THE MET TYROSINE KINASE INHIBITOR CRIZOTINIB (PF-02341066) IN GASTRIC CANCER POSITIVE FOR MET AMPLIFICATION

W. Okamoto, I. Okamoto, T. Arao, S. -i. Nishina, S. Ueda, H. Kawakami, K. Yanagihara, T. Kurata, K. Nishio, K. Nakagawa

ANNALS OF ONCOLOGY　23　84-84　2012年10月

ISSN： 0923-7534
POSTPROGRESSION SURVIVAL FOR FIRST-LINE CHEMOTHERAPY IN PATIENTS WITH ADVANCED GASTRIC CANCER

H. Kawakami, I. Okamoto, H. Hayashi, M. Taguri, S. Morita, K. Nakagawa

ANNALS OF ONCOLOGY　23　95-95　2012年10月

ISSN： 0923-7534
PHARMACOKINETICS (PK) AND SAFETY OF TESETAXEL, A NOVEL ORAL TAXANE, IN JAPANESE PATIENTS (PTS) WITH ADVANCED SOLID TUMORS

K. Tanaka, T. Kurata, Y. Fujisaka, H. Kawakami, H. Hayashi, T. Cousin, W. Okamoto, T. Kudoh, T. Satoh, K. Nakagawa

ANNALS OF ONCOLOGY　23　167-167　2012年9月

ISSN： 0923-7534
MET遺伝子増幅を有する胃癌に対するクリゾチニブの抗腫瘍効果(Antitumor action of the MET tyrosine kinase inhibitor crizotinib in gastric cancer positive for MET amplification)

岡本渉, 岡本勇, 荒尾徳三, 坂井和子, 岡本邦男, 川上尚人, 金田裕靖, 仁科慎一, 鶴谷純司, 倉田宝保, 柳原五吉, 西尾和人, 中川和彦

日本癌学会総会記事　71回　466-466　2012年8月
出版者・発行元：日本癌学会
ISSN： 0546-0476
アンスラまたはタキサン耐性のHER2陽性乳癌に対するCPT‐11+trastuzumab併用療法におけるfeasibility trial

西田幸弘, 富永修盛, 増田慎三, 鶴谷純司, 佐藤太朗, 川上尚人, 岡本勇, 森本卓, 山口正秀, 松並展輝, 新井貴志, 坂本純一, 中山貴寛, 中川和彦

日本乳癌学会学術総会プログラム・抄録集　20th　316-316　2012年5月30日
出版者・発行元： (一社)日本乳癌学会
抗悪性腫瘍薬の治験は安全か相別SAE発生率の検討

清田秀美, 藤阪保仁, 川上尚人, 田中薫, 工藤敏啓, 鶴谷純司, 宮崎昌樹, 岡本勇, 倉田宝保, 中川和彦

日本内科学会雑誌　101　(Suppl.)　316-316　2012年2月
出版者・発行元： (一社)日本内科学会
ISSN： 0021-5384

eISSN： 1883-2083
EML4‐ALK陽性進行非小細胞肺癌における,初回白金併用化学療法の治療効果の検討

武田真幸, 岡本勇, 坂井和子, 川上尚人, 西尾和人, 中川和彦

日本癌治療学会学術集会(CD-ROM)　50th　(3)　ROMBUNNO.PD18-03-1272　2012年
出版者・発行元： (一社)日本癌治療学会
ISSN： 0021-4671
マグネシウム補充によるシスプラチン関連腎障害の抑制効果の検討

木寺康裕, 川上尚人, 谷崎潤子, 田中薫, 上田眞也, 岡本渉, 仁科慎一, 金田裕靖, 藤原季美子, 千葉康敬, 西田升三, 山添譲, 倉田宝保, 岡本勇, 中川和彦

日本癌治療学会学術集会(CD-ROM)　50th　(3)　ROMBUNNO.OS29-5-974　2012年
出版者・発行元： (一社)日本癌治療学会
ISSN： 0021-4671
進化するがん免疫療法(ワクチン療法,細胞療法,抗体療法)抗体療法 3)固形がんの抗体療法

川上尚人, 岡本勇

月刊腫瘍内科　8　(5)　514-522　2011年11月28日
出版者・発行元：科学評論社
ISSN： 1881-6568
切除不能進行胆道癌に対するCDDP+GEM療法

川上尚人, 上田眞也, 工藤敏啓, 岡本渉, 中川和彦

日本消化器病学会雑誌　108　A897　2011年9月15日

ISSN： 0446-6586
切除不能胆道癌に対するCDDP+GEM療法

川上尚人, 上田眞也, 工藤敏啓, 岡本渉, 仁科慎一, 中川和彦

日本癌治療学会誌　46　(2)　671　2011年9月13日

ISSN： 0021-4671
前化学療法歴を有する切除不能・再発胆道癌に対するTS-1療法

上田眞也, 佐藤太郎, 仁科慎一, 川上尚人, 田中薫, 清田秀美, 岡本渉, 金田裕靖, 工藤敏啓, 藤阪保仁, 鶴谷純司, 宮崎昌樹, 倉田宝保, 岡本勇, 中川和彦

日本癌治療学会誌　46　(2)　672-672　2011年9月
出版者・発行元： (一社)日本癌治療学会
ISSN： 0021-4671
切除不能進行食道がんに対する化学放射線併用療法

上田眞也, 川上尚人, 中川和彦, 牧村ちひろ, 松岡弘道, 小山冨美子, 林真理子

日本緩和医療学会学術大会プログラム・抄録集　16th　268　2011年6月27日
悪性狭窄に対する緩和的TTSステント留置に関する検討

川上尚人, 上田眞也, 工藤敏啓, 佐藤太郎, 中川和彦

日本緩和医療学会学術大会プログラム・抄録集　16th　389　2011年6月27日
大腸癌の治療戦略化学療法切除不能進行・再発大腸癌に対するFOLFOXIRI療法

川上尚人, 佐藤太郎, 中川和彦

日本臨床　69　439-445　2011年4月20日

ISSN： 0047-1852
PRIME試験/20050181試験:大腸がん化学療法パニツムマブの最適な使用法とは何か?

川上尚人, 佐藤太郎

臨床腫瘍プラクティス　29-37　2011年3月10日

ISSN： 1880-3083
当院で施行したXP療法の5例の経験

川上尚人, 佐藤太郎, 上田眞也, 工藤敏啓, 藤阪保仁, 宮崎昌樹, 鶴谷純司, 倉田宝保, 岡本勇, 中川和彦

日本胃癌学会総会記事　83回　221-221　2011年3月
出版者・発行元： (一社)日本胃癌学会
Paclitaxel療法後Docetaxel療法を行った進行再発胃癌14例の検討

工藤敏啓, 佐藤太郎, 川上尚人, 上田眞也, 宮崎昌樹, 藤坂保仁, 鶴谷純司, 倉田宝保, 岡本勇, 中川和彦

日本消化管学会総会学術集会プログラム・抄録集　7th　288　2011年
切除不能・進行再発胃癌に対するXP療法の検討

川上尚人, 上田眞也, 工藤敏啓, 佐藤太郎, 岡部崇記, 林秀敏, 清田秀美, 寺嶋応顕, 武田真幸, 藤阪保仁, 宮崎昌樹, 鶴谷純司, 倉田宝保, 岡本勇, 中川和彦

日本臨床腫瘍学会学術集会プログラム・抄録集　9th　330　2011年
イマチニブ耐性GISTに対しスニチニブを使用した4例の経験

川上尚人, 佐藤太郎, 上田眞也, 工藤敏啓, 岡本勇, 倉田宝保, 鶴谷純司, 宮崎昌樹, 藤阪保仁, 中川和彦

日本消化管学会総会学術集会プログラム・抄録集　7th　331　2011年

ISSN： 2189-9037
根治切除・照射不能進行食道がんに対する化学療法と局所食道放射線併用療法

上田眞也, 佐藤太郎, 川上尚人, 工藤敏啓, 林秀敏, 清田秀美, 武田真幸, 宮崎昌樹, 岡本勇, 中川和彦

日本消化管学会総会学術集会プログラム・抄録集　7th　287　2011年
Paclitaxel療法後Docetaxel療法を行った進行再発胃癌14例の検討

工藤敏啓, 佐藤太郎, 川上尚人, 上田眞也, 岡本渉, 岡部崇記, 寺島応顕, 清田秀美, 武田真幸, 宮崎昌樹, 藤阪保仁, 鶴谷純司, 倉田宝保, 岡本勇, 中川和彦

日本臨床腫瘍学会学術集会プログラム・抄録集　9th　426　2011年
イマチニブ耐性GISTに対しスニチニブを使用した4例の経験

川上尚人, 佐藤太郎, 中川和彦

日本癌治療学会誌　45　(2)　407　2010年9月21日

ISSN： 0021-4671
消化管粘膜下腫瘍に対する超音波内視鏡下穿刺生検法(EUS‐FNAB)の検討

松田史博, 岡部純弘, 竹田治彦, 犬塚義, 中島潤, 金坂卓, 恵荘裕嗣, 坂本梓, 邊見慎一郎, 石川哲郎, 川上尚人, 波多野貴昭, 松尾裕央, 斎藤澄夫, 西川浩樹, 津村嗣彦, 喜多竜一, 木村達, 大崎往夫, 若狭朋子

Gastroenterol Endosc　52　(Supplement 2)　2427-2427　2010年9月10日
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
根治切除・照射不能進行食道がんに対する化学療法と局所食道放射線併用療法

上田眞也, 佐藤太郎, 川上尚人, 田中薫, 林秀敏, 清田秀美, 武田真幸, 東公一, 米坂仁雄, 藤阪保仁, 鶴谷純司, 宮崎昌樹, 岡本勇, 倉田宝保, 中川和彦

日本癌治療学会誌　45　(2)　990-990　2010年9月
出版者・発行元： (一社)日本癌治療学会
ISSN： 0021-4671
消化器癌の分子標的治療胃癌に対する抗体療法

川上尚人, 佐藤太郎

月刊消化器内科　51　(1)　91-98　2010年7月28日
出版者・発行元：科学評論社
ISSN： 1884-2895
小腸癌術後再発が疑われたクローン病患者の止血困難な下血に対しインフリキシマブを投与し急激な癌の増悪を認めた1例

川上尚人, 津村剛彦, 圓尾隆典, 青山芳樹, 新宅雅幸

Prog Med　30　(7)　2021-2024　2010年7月10日

ISSN： 0287-3648
当院における直近10年間の劇症肝炎症例23例の検討

犬塚義, 竹田治彦, 金坂卓, 中島潤, 松田史博, 恵荘裕嗣, 坂本梓, 邉見慎一郎, 石川哲郎, 川上尚人, 斎藤澄夫, 波多野貴昭, 松尾裕央, 西川浩樹, 津村剛彦, 喜多竜一, 圓尾隆典, 岡部純弘, 木村達, 大崎往夫, 橋本まち子

肝臓　51　(Supplement 1)　A386-A386　2010年4月30日
出版者・発行元： (一社)日本肝臓学会
ISSN： 0451-4203

eISSN： 1881-3593
当院における肝細胞癌に対する経皮的ラジオ波熱凝固療法(RFA)10年間の治療成績

木村達, 大崎往夫, 喜多竜一, 西川浩樹, 斎藤澄夫, 松尾裕央, 坂本梓, 恵荘裕嗣, 中島潤, 松田史博, 邉見慎一郎, 竹田治彦, 犬塚義, 川上尚人, 石川哲朗, 波多野貴昭, 岡部純弘

肝臓　51　(Supplement 1)　A148-A148　2010年4月30日
出版者・発行元： (一社)日本肝臓学会
ISSN： 0451-4203

eISSN： 1881-3593
B型慢性肝疾患の初回肝癌根治後症例に対する核酸アナログ投与の有無と全生存期間・無再発期間・無再発生存率についての検討

犬塚義, 大崎往夫, 竹田治彦, 金坂卓, 中島潤, 松田史博, 恵荘裕嗣, 坂本梓, 邉見慎一郎, 石川哲郎, 川上尚人, 斎藤澄夫, 波多野貴昭, 松尾裕央, 西川浩樹, 津村剛彦, 喜多竜一, 圓尾隆典, 岡部純弘, 木村達

肝臓　51　(Supplement 1)　S146-A146　2010年4月30日
出版者・発行元： (一社)日本肝臓学会
ISSN： 0451-4203

eISSN： 1881-3593
C型慢性肝炎に対するRBV併用IFN療法による肝発癌抑制の検討―AFPは肝発癌抑制のsurrogateマーカーとなり得るか―

中島潤, 竹田治彦, 犬塚義, 松田史博, 金坂卓, 坂本梓, 恵荘裕嗣, 邉見慎一郎, 石川哲郎, 川上尚人, 波多野貴昭, 松尾裕央, 斎藤澄夫, 西川浩樹, 津村剛彦, 圓尾隆典, 喜多竜一, 岡部純弘, 木村達, 大崎往夫

肝臓　51　(Supplement 1)　A124-A124　2010年4月30日
出版者・発行元： (一社)日本肝臓学会
ISSN： 0451-4203

eISSN： 1881-3593
当科における胆管内乳頭状腫瘍(IPNB)3例の検討

松田史博, 岡部純弘, 中島潤, 金坂卓, 恵荘裕嗣, 坂本梓, 邊見慎一郎, 石川哲郎, 川上尚人, 波多野貴昭, 松尾裕央, 斎藤澄夫, 西川浩樹, 津村剛彦, 喜多竜一, 圓尾隆典, 木村達, 大崎往夫, 若狭朋子

Gastroenterol Endosc　52　(Supplement 1)　971　2010年4月10日

ISSN： 0387-1207
インジゴカルミン撒布で認識できず拡大内視鏡観察で発見し得たESD後早期胃癌2症例

金坂卓, 犬塚義, 竹田治彦, 中島潤, 松田史博, 恵荘裕嗣, 坂本梓, 邊見慎一郎, 石川哲朗, 川上尚人, 齋藤澄夫, 波多野貴昭, 松尾裕央, 西川浩樹, 津村剛彦, 喜多竜一, 岡部純弘, 木村達, 圓尾隆典, 大崎往夫, 若狭朋子

Gastroenterol Endosc　52　(Supplement 1)　1082-1082　2010年4月10日
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
悪性十二指腸狭窄に対するステント留置術に関する検討

中島潤, 犬塚義, 竹田治彦, 松田史博, 金坂卓, 石川哲郎, 坂本梓, 恵荘裕嗣, 邉見慎一郎, 川上尚人, 波多野貴昭, 松尾裕央, 齋藤澄夫, 西川浩樹, 喜多竜一, 木村達, 津村剛彦, 圓尾隆典, 岡部純弘, 大崎往夫

Gastroenterol Endosc　52　(Supplement 1)　1041-1041　2010年4月10日
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
当院におけるsorafenibの使用経験.その現状と問題点

邉見慎一郎, 大崎往夫, 木村達, 岡部純弘, 圓尾隆典, 喜多竜一, 津村剛彦, 西川浩樹, 松尾裕央, 齋藤澄夫, 波多野貴昭, 川上尚人, 石川哲朗, 恵荘裕嗣, 坂本梓, 中嶋潤, 松田史博, 金坂卓, 犬塚義, 竹田治彦

日本消化器病学会雑誌　107　(臨増総会)　A439-A439　2010年3月15日
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
肝細胞癌に対するTAI,TACE後治療効果判定におけるソナゾイド造影超音波の有用性

坂本梓, 大崎往夫, 木村達, 池田敦之, 谷口敏勝, 金坂卓, 松田史博, 中島潤, 永田嘉昭, 南晶洋, 恵荘裕嗣, 川上尚人, 波多野貴昭, 松尾裕央, 齋藤澄夫, 中辻正人, 西川浩樹, 岡部純弘, 喜多竜一

肝臓　51　(7)　361-370　2010年
出版者・発行元：一般社団法人日本肝臓学会
DOI： 10.2957/kanzo.51.361 　

ISSN： 0451-4203
ゲムシタビンによる薬剤性肺障害が疑われた膵胆道癌の9例

津村剛彦, 松尾裕央, 圓尾隆典, 川上尚人, 波多野貴昭, 坂本梓, 邉見慎一郎, 恵荘裕嗣, 斎藤澄夫, 西川浩樹, 喜多竜一, 岡部純弘, 木村達, 網谷良一, 大崎往夫

日本臨床腫瘍学会学術集会プログラム・抄録集　8th　266　2010年
肝臓原発と思われるOsteosarcomaの一例

邉見慎一郎, 若狭朋子, 竹田治彦, 犬塚義, 松田史博, 金坂卓, 中島潤, 坂本梓, 恵荘裕嗣, 川上尚人, 斎藤澄夫, 波多野貴昭, 松尾裕央, 西川浩樹, 喜多竜一, 岡部純弘, 木村達, 大崎往夫

肝臓　50　(Supplement 3)　A766　2009年11月5日

ISSN： 0451-4203
Sonazoid造影USの門脈優位相で染影像を呈した高分化肝細胞癌の一例

齋藤澄夫, 喜多竜一, 竹田治彦, 犬塚義, 金坂卓, 中島潤, 松田史博, 坂本梓, 邊見慎一郎, 恵荘裕嗣, 川上尚人, 波多野貴昭, 松尾裕央, 西川浩樹, 津村剛彦, 圓尾隆典, 岡部純弘, 木村達, 大崎往夫, 若狭朋子

肝臓　50　(Supplement 3)　A750　2009年11月5日

ISSN： 0451-4203
S‐1+CDDPが有効であった膵原発が疑われる腹腔内腫瘍多発肝転移の1例

川上尚人, 松田史博, 金坂卓, 中島潤, 坂本梓, 恵荘裕嗣, 波多野貴昭, 松尾裕央, 斎藤澄夫, 西川浩樹, 津村剛彦, 喜多竜一, 圓尾隆典, 岡部純弘, 木村達, 大崎往夫

日本消化器病学会雑誌　106　A949　2009年9月15日

ISSN： 0446-6586
2nd lineにてFOLFIRI+cetuximabが著効した腹膜播種および肝転移再発大腸がんの1例

川上尚人, 金澤旭宣

日本癌治療学会誌　44　(2)　897　2009年9月14日

ISSN： 0021-4671
胃ESD後潰瘍からの後出血は予防できるか

圓尾隆典, 金坂卓, 波多野貴昭, 津村剛彦, 大崎往夫, 松田史博, 中島潤, 川上尚人, 坂本梓, 恵荘裕嗣, 岡部純弘, 木村達

Gastroenterol Endosc　51　(Supplement 2)　2202　2009年9月10日

ISSN： 0387-1207
Collagenous colitis7例の検討―縦走潰瘍はcollagenous colitisの特徴か―

齋藤澄夫, 坂本梓, 恵荘裕嗣, 永田嘉昭, 南晶洋, 川上尚人, 松尾裕夫, 波多野貴昭, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 喜多竜一, 圓尾隆典, 岡部純弘, 木村達, 大崎往夫, 若狭朋子

Gastroenterol Endosc　51　(Supplement 2)　2253　2009年9月10日

ISSN： 0387-1207
肝癌治療前後における腫瘍マーカーの変化およびRFA後治療効果判定との関連性の検討

恵荘裕嗣, 中島潤, 松田史博, 金坂卓, 坂本梓, 川上尚人, 松尾裕央, 齋藤澄夫, 西川浩樹, 喜多竜一, 岡部純弘, 木村達, 大崎往夫

肝臓　50　(Supplement 2)　A562　2009年9月10日

ISSN： 0451-4203
臨床症状と内視鏡所見に乖離のみられた潰瘍性大腸炎の疑診例

金坂卓, 津村剛彦, 中辻正人, 恵荘裕嗣, 坂本梓, 永田嘉昭, 川上尚人, 山中伸一, 齋藤澄夫, 西島規浩, 波多野貴昭, 松尾裕央, 松村真生子, 池田敦之, 西川浩樹, 岡部純弘, 喜多竜一, 圓尾隆典, 木村達, 大崎往夫

Prog Med　29　(7)　1869-1872　2009年7月10日

ISSN： 0287-3648
肝細胞癌根治後のC型慢性肝疾患に対するPEG‐IFNα2b/Ribavirin併用療法の有用性に関する検討

齋藤澄夫, 木村達, 坂本梓, 恵荘裕嗣, 南晶洋, 永田嘉昭, 山中伸一, 川上尚人, 波多野貴昭, 松尾裕央, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 喜多竜一, 岡部純弘, 圓尾隆典, 大崎往夫

肝臓　50　(Supplement 1)　A205　2009年4月30日

ISSN： 0451-4203
悪性消化管閉塞に対するオクトレオチドの使用状況と問題点

圓尾隆典, 津村剛彦, 波多野貴昭, 松田史博, 中島潤, 金坂卓, 南晶洋, 坂本梓, 恵荘裕嗣, 川上尚人, 永田嘉昭, 中辻正人, 池田敦之, 松尾裕央, 斎藤澄夫, 西川浩樹, 喜多竜一, 岡部純弘, 木村達, 大崎往夫

日本消化器病学会雑誌　106　A152　2009年3月20日

ISSN： 0446-6586
小腸がん術後再発が疑われたCrohn病患者の止血困難な下血に対しInfliximabを投与し急激ながんの増悪を認めた1例

川上尚人, 金坂卓, 中島潤, 松田史博, 永田嘉昭, 坂本梓, 恵荘裕嗣, 南晶洋, 波多野貴昭, 松尾裕央, 斎藤澄夫, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 喜多竜一, 圓尾隆典, 岡部純広, 木村達, 大崎往夫

日本消化器病学会雑誌　106　A427　2009年3月20日

ISSN： 0446-6586
ここまで使える経鼻内視鏡経鼻内視鏡だからできる胃潰瘍止血術

圓尾隆典, 松尾裕央, 津村剛彦, 波多野貴昭, 川上尚人, 那須章洋

消化器内視鏡　21　(1)　109-114　2009年1月25日

ISSN： 0915-3217
ソナゾイド造影超音波による肝細胞癌のRFA後治療効果判定-造影CTとの比較-

池田敦之, 木村達, 坂本梓, 永田嘉昭, 恵荘裕嗣, 川上尚人, 齋藤澄夫, 波多野貴昭, 松尾裕央, 西島規浩, 中辻正人, 西川浩樹, 喜多竜一, 岡部純弘, 谷口敏勝, 大崎往夫

肝臓　50　(7)　362-370　2009年
出版者・発行元：一般社団法人日本肝臓学会
DOI： 10.2957/kanzo.50.362 　

ISSN： 0451-4203
Gemcitabineによる薬剤性肺障害が疑われた膵胆道癌の7例

津村剛彦, 松尾裕央, 圓尾隆典, 川上尚人, 波多野貴昭, 齋藤澄夫, 西島規浩, 中辻正人, 池田敦之, 西川浩樹, 喜多竜一, 岡部純弘, 木村達, 網谷良一, 大崎往夫

癌と化学療法　36　(5)　785-788　2009年
出版者・発行元： Japanese Journal of Cancer and Chemotherapy Publishers Inc.
ISSN： 0385-0684
IVRにおけるFPD(Flat Panel Detecter)を用いたLCI(Low Contrast Imaging)の有用性

山中伸一, 坂本梓, 恵荘裕嗣, 永田嘉昭, 川上尚人, 松村真生子, 波多野貴昭, 西島規浩, 松尾裕央, 斎藤澄夫, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 岡部純弘, 岡田光正, 芦田信示, 圓尾隆典, 喜多竜一, 木村達, 大崎往夫

IVR　23　(4)　416　2008年10月1日

ISSN： 1340-4520
ゲムシタビン治療中に肺障害を発症した膵胆道癌の4症例

津村剛彦, 松尾裕央, 圓尾隆典, 川上尚人, 波多野貴昭, 齋藤澄夫, 中辻正人, 池田敦之, 坂本梓, 永田嘉昭, 恵荘裕嗣, 喜多竜一, 岡部純弘, 木村達, 大崎往夫

日本消化器病学会雑誌　105　A915　2008年9月15日

ISSN： 0446-6586
胃静脈瘤破裂に対する3D‐DSAの検討

山中伸一, 坂本梓, 恵荘裕嗣, 永田嘉昭, 川上尚人, 波多野貴昭, 松尾裕央, 斎藤澄夫, 中辻正人, 池田敦之, 西川浩樹, 塩崎俊城, 津村剛彦, 圓尾隆典, 喜多竜一, 岡部純弘, 木村達, 大崎往夫

日本消化器病学会雑誌　105　A845　2008年9月15日

ISSN： 0446-6586
血清hTERT mRNA発現量測定の肝癌患者における臨床的有用性についての検討

恵荘裕嗣, 坂本梓, 永田嘉昭, 川上尚人, 山中伸一, 波多野貴昭, 松尾裕央, 齋藤澄夫, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 圓尾隆典, 岡部純弘, 木村達, 大崎往夫, 汐田剛史

肝臓　49　(Supplement 2)　A571　2008年9月5日

ISSN： 0451-4203
胃癌に対する粘膜下層剥離術(ESD)の現況と問題点

圓尾隆典, 波多野貴昭, 津村剛彦, 松田史博, 中島潤, 金坂卓, 恵荘裕嗣, 坂本梓, 永田嘉昭, 南晶洋, 川上尚人, 山中伸一, 中辻正人, 西川浩樹, 松尾裕央, 齋藤澄夫, 大崎往夫

日赤医学　60　(1)　208　2008年9月1日

ISSN： 0387-1215
C型慢性肝炎に対するPEG‐IFNα2b+Ribavirin併用療法におけるSVR・SBRに寄与する因子の検討

池田敦之, 坂本梓, 恵荘裕嗣, 永田嘉昭, 山中伸一, 川上尚人, 波多野貴昭, 松尾裕央, 齋藤澄夫, 西島規浩, 中辻正人, 西川浩樹, 喜多竜一, 岡部純弘, 木村達, 大崎往夫

肝臓　49　(Supplement 1)　A299　2008年4月30日

ISSN： 0451-4203
経鼻内視鏡による直視胆道鏡下に砕石できた総胆管大結石の一例

坂本梓, 圓尾隆典, 恵荘裕嗣, 永田嘉昭, 川上尚人, 山中伸一, 齋藤澄夫, 西島規浩, 波多野貴昭, 松尾裕央, 池田敦之, 中辻正人, 西川浩樹, 津村剛彦, 岡部純弘, 喜多竜一, 木村達, 大崎往夫

Gastroenterol Endosc　50　(Supplement 1)　904　2008年4月15日

ISSN： 0387-1207
RFA施行時におけるMulti‐phase Real‐time Virtual Sonographyの有用性

西島規浩, 恵荘裕嗣, 坂本梓, 永田嘉昭, 川上尚人, 山中伸一, 松村真生子, 波多野貴昭, 斉藤澄夫, 松尾裕央, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 喜多竜一, 圓尾隆典, 岡部純弘, 木村達, 大崎往夫

日本消化器病学会雑誌　105　A216　2008年3月20日

ISSN： 0446-6586
肝細胞癌に対する血管内治療における,FPDを用いたLCI(Cone‐Beam CT)の有用性並びに今後についての検討

山中伸一, 坂本梓, 恵荘裕嗣, 永田嘉昭, 川上尚人, 波多野貴昭, 西島規浩, 松尾裕央, 齋藤澄夫, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 岡部純弘, 岡田光正, 芦田信示, 喜多竜一, 圓尾隆典, 木村達, 大崎征夫

日本消化器病学会雑誌　105　A415　2008年3月20日

ISSN： 0446-6586
EMR後再発胃癌のESD後に肝被膜下膿瘍を発症した1例

圓尾隆典, 恵荘裕嗣, 坂本梓, 永田嘉昭, 川上尚人, 山中伸一, 波多野貴昭, 西島規浩, 松尾裕央, 斉藤澄夫, 中辻正人, 池田敦之, 西川浩樹, 津村剛彦, 喜多竜一, 岡部純弘, 木村達, 大崎往夫, 辻賢太郎

日本消化器病学会雑誌　105　A353　2008年3月20日

ISSN： 0446-6586
TAI後のHCCにSonazoid造影で動脈血流の流入が確認された1例

坂本梓, 木村達, 池田敦之, 谷口敏勝, 山中伸一, 川上尚人, 西島規浩, 齋藤澄夫, 波多野貴昭, 松尾裕央, 中辻正人, 西川浩樹, 岡部純弘, 喜多竜一, 大崎往夫

超音波医学　35　(2)　253　2008年3月15日

ISSN： 1346-1176
コロナ様濃染を認めた限局性結節性過形成(FNH)の1症例

喜多竜一, 中辻正人, 西島規浩, 川上尚人, 波多野貴昭, 松尾裕央, 齋藤澄夫, 池田敦之, 那須章洋, 西川浩樹, 木村達, 大崎往夫, 中島収

日本消化器病学会雑誌　105　(4)　550-557　2008年

DOI： 10.11405/nisshoshi.105.550 　

ISSN： 0446-6586
肝細胞癌に対するRFAにおける効果判定基準の提唱‐局所再発率の検討から‐

西島規浩, 大崎往夫, 喜多竜一, 恵荘祐嗣, 山中伸一, 川上尚人, 斎藤澄夫, 波多野貴昭, 松尾裕央, 中辻正人, 池田敦之, 西川浩樹, 圓尾隆典, 岡部純弘, 木村達

肝臓　49　(5)　192-199 (J-STAGE)-199　2008年
出版者・発行元：一般社団法人日本肝臓学会
DOI： 10.2957/kanzo.49.192 　

ISSN： 0451-4203

詳細を見る詳細を閉じる

【目的】RFA後の治療効果判定として結節周囲に得られた凝固域の程度に応じて症例を分類し，それぞれの局所再発率を求めその意義を検討する．【方法】RVS誘導下RFAを施行した77症例99結節を対象とした．結節周囲に得られた凝固域の程度に応じて根治度（Radicality grade, R grade）を4段階（R0, R1, R2, R3）に定義した．根治度ごとの累積局所再発率を求めるとともに，局所再発に寄与する因子を解析した．また，再発症例において，再発部位における治療後腫瘍との距離を検討した．【結果】根治度別の累積局所再発率は，2年で，R3：3.7%, R2：13.6%, R1：52.6%, R0：66.7%であった．多変量解析では根治度のみが局所再発に寄与する独立した有意な因子として検出された．局所再発した25例のうち20例は，治療結節外側の凝固域が5 mm未満の部位に再発を認めた．【結論】RFAの良好な治療効果判定基準として，全周に5 mm以上の凝固域を獲得することが望まれる．<br>
急性腎不全を呈したLemierre症候群の1例

岩本善嵩, 川上尚人, 岸史, 宮本昌彦, 南方保

日本内科学会雑誌　96　(12)　2792-2793　2007年12月10日

DOI： 10.2169/naika.96.2792 　

ISSN： 0021-5384
悪性腹膜中皮腫の1例

池田敦之, 津村剛彦, 川上尚人, 坂本康明, 西島規浩, 松尾裕央, 斎藤澄夫, 波多野貴昭, 中辻正人, 那須章洋, 西川浩樹, 喜多竜一, 谷口敏勝, 木村達, 大崎往夫

超音波医学　34　(6)　621-622　2007年11月15日

ISSN： 1346-1176
当院における非B非C型肝細胞癌の検討

木村達, 大崎往夫, 喜多竜一, 西川浩樹, 池田敦之, 岡部純弘, 中辻正人, 齋藤澄夫, 西島規浩, 波多野貴昭, 松尾裕央, 川上尚人, 山中伸一, 恵荘裕嗣, 坂本梓, 永田嘉昭

新薬と臨床　56　(11)　1893-1894　2007年11月10日

ISSN： 0559-8672
肝細胞癌におけるソナゾイド造影超音波検査の有用性

池田敦之, 木村達, 坂本梓, 恵荘裕嗣, 永田嘉昭, 山中伸一, 川上尚人, 斉藤澄夫, 西島規浩, 松尾裕央, 波多野貴昭, 中辻正人, 西川浩樹, 喜多竜一, 岡部純弘, 大崎往夫

肝臓　48　(Supplement 3)　A548　2007年11月5日

ISSN： 0451-4203
腫瘤血洞から直接類洞に流出する血行路とコロナ様濃染の出現についての考察

喜多竜一, 西島規浩, 中辻正人, 恵荘裕嗣, 坂本梓, 山中伸一, 永田嘉昭, 川上尚人, 松尾裕央, 斎藤澄夫, 池田敦之, 西川浩樹, 木村達, 大崎往夫, 中島収

肝臓　48　(Supplement 3)　A566　2007年11月5日

ISSN： 0451-4203
Peritumoral spared areaにリング様濃染を認めたFNH様過形成結節の一例

西島規浩, 喜多竜一, 川上尚人, 山中伸一, 松尾裕央, 斉藤澄夫, 波多野貴明, 中辻正人, 池田敦之, 西川浩樹, 岡部純弘, 木村達, 大崎往夫

肝臓　48　(Supplement 3)　A629　2007年11月5日

ISSN： 0451-4203
血行動態の異なる大型結節が混在し,その経過を長期観察しえた肝細胞癌の1症例

齋藤澄夫, 喜多竜一, 坂本梓, 恵荘裕嗣, 永田嘉昭, 川上尚人, 山中伸一, 西島規浩, 松尾裕央, 波多野貴昭, 中辻正人, 池田敦之, 西川浩樹, 岡部純弘, 木村達, 大崎往夫

肝臓　48　(Supplement 3)　A538　2007年11月5日

ISSN： 0451-4203
慢性B型肝障害に対するLamivudine長期投与によりHBs Agが陰性化した三例

松尾裕央, 大崎往夫, 坂本梓, 恵荘裕嗣, 永田嘉昭, 川上尚人, 山中伸一, 波多野貴昭, 齋藤澄夫, 西島規浩, 池田敦之, 中辻正人, 西川浩樹, 喜多竜一, 木村達

肝臓　48　(Supplement 3)　A519　2007年11月5日

ISSN： 0451-4203
C型慢性肝炎に対するPEG‐IFNα2b+Ribavirin併用療法におけるSVRに寄与する因子の検討

池田敦之, 川上尚人, 齋藤澄夫, 松尾裕央, 波多野貴昭, 西島規浩, 中辻正人, 那須章洋, 西川浩樹, 喜多竜一, 木村達, 大崎往夫

肝臓　48　(Supplement 2)　A412　2007年9月15日

ISSN： 0451-4203
腫瘤血洞から直接類洞に流出する血行路とコロナ様濃染の出現についての考察

喜多竜一, 西島規浩, 中辻正人, 川上尚人, 坂本康明, 松尾裕央, 斎藤澄夫, 波多野貴昭, 池田敦之, 那須章洋, 西川浩樹, 木村達, 大崎往夫, 中島収

肝臓　48　(5)　246-248　2007年5月25日
出版者・発行元：一般社団法人日本肝臓学会
DOI： 10.2957/kanzo.48.246 　

ISSN： 0451-4203

詳細を見る詳細を閉じる

Corona enhancements on single level dynamic CTHA (sCTHA) images are thought to be characteristic of hypervascular metastatic liver tumors and HCCs. Herein we present two cases (an FNH and a nodule-in-nodule type HCC) in which sCTHA images showed corona enhancements. In the literature, venous and sinusoidal drainage pathways have been confirmed histopathologically in FNH. We presume that drainage flow occurs mainly through a hepatic venous pathway in FNH and that drainage flow via a sinusoidal pathway is faint and may be visible only when the amount of drainage flow becomes large followed by an increase in tumor size. Moreover, a corona enhancement was also seen in a HCC that lacked a capsule but had a replacing growth pattern. A drainage pathway via a sinusoid may be causing the emergence of a corona enhancement on sCTHA images in the cases discussed herein.<br>
ネフローゼを契機に発見されたクローン病に続発した全身アミロイドーシスの1例

川上尚人, 岩本善嵩, 南方保, 那須章洋, 圓尾隆典, 大崎往夫, 新宅雅幸

Pharma Med　25　(5)　176-177　2007年5月10日

ISSN： 0289-5803
CTAPにて濃染する結節21症例の検討

喜多竜一, 那須章洋, 池田敦之, 西島規浩, 松尾裕央, 坂本康明, 齋藤澄夫, 波多野貴昭, 西川浩樹, 木村達, 川上尚人, 中辻正人, 大崎往夫, 大部誠

肝臓　48　(Supplement 1)　A110　2007年4月25日

ISSN： 0451-4203
当院におけるB型慢性肝疾患に対するLamivudine,Adefovir dipivoxil療法の検討

松尾裕央, 大崎往夫, 坂本康明, 川上尚人, 波多野貴昭, 齋藤澄夫, 西島規浩, 中辻正人, 池田敦之, 那須章洋, 西川浩樹, 喜多竜一, 木村達

肝臓　48　(Supplement 1)　A254　2007年4月25日

ISSN： 0451-4203
リング様濃染を認めたFNHの1例

中辻正人, 喜多竜一, 川上尚人, 坂本康明, 齋藤澄夫, 西島規浩, 波多野貴昭, 松尾裕央, 池田敦之, 那須章洋, 西川浩樹, 木村達, 大崎往夫, 中島収

肝臓　48　(Supplement 1)　A236　2007年4月25日

ISSN： 0451-4203
門脈血流減少度の評価による肝細胞癌境界病変脱分化推定の可能性

喜多竜一, 西島規浩, 川上尚人, 松尾裕央, 坂本康明, 齋藤澄夫, 波多野貴昭, 中辻正人, 池田敦之, 那須章洋, 西川浩樹, 木村達, 大崎往夫, 坂元亨宇

肝臓　48　(Supplement 1)　A62　2007年4月25日

ISSN： 0451-4203
CTAPにて濃染する多発結節を認めた特発性門脈圧亢進症の一例

池田敦之, 喜多竜一, 川上尚人, 坂本康明, 西島規浩, 松尾裕央, 齋藤澄夫, 波多野貴昭, 中辻正人, 那須章洋, 西川浩樹, 木村達, 大崎往夫, 大部誠

肝臓　48　(Supplement 1)　A236　2007年4月25日

ISSN： 0451-4203
C型慢性肝炎に対するPEG‐IFNα2b+ribavirin併用療法における無効,再燃例の特徴

那須章洋, 川上尚人, 坂本康明, 松尾裕央, 波多野貴昭, 西島規浩, 齋藤澄夫, 池田敦之, 中辻正人, 西川浩樹, 喜多竜一, 木村達, 大崎往夫

肝臓　48　(Supplement 1)　A258　2007年4月25日

ISSN： 0451-4203
止血困難例に対する高張食塩水エピネフリン局注・アルゴンプラズマ凝固併用療法の有用性

波多野貴昭, 津村剛彦, 圓尾隆典, 辻賢太郎, 松尾裕央, 齋藤澄夫, 西島規浩, 坂本康明, 川上尚人, 中辻正人, 池田敦之, 那須章洋, 西川浩樹, 喜多竜一, 木村達, 大崎往夫

Gastroenterol Endosc　49　(Supplement 1)　964　2007年4月5日

ISSN： 0387-1207
当院におけるB型慢性肝疾患に対するLamivudine,Adefovir dipivoxil療法の検討

松尾裕央, 大崎往夫, 坂本康明, 川上尚人, 波多野貴昭, 齋藤澄夫, 西島規浩, 中辻正人, 池田敦之, 那須章洋, 西川浩樹, 辻賢太郎, 津村剛彦, 喜多竜一, 圓尾隆典, 木村達

日本消化器病学会雑誌　104　A109　2007年3月20日

ISSN： 0446-6586
Peritumoral spared areaにリング様濃染を認めたFNH様過形成結節の1例

西島規浩, 喜多竜一, 川上尚人, 坂本康明, 松尾裕央, 斎藤澄夫, 波多野貴昭, 中辻正人, 池田敦之, 那須章洋, 西川浩樹, 木村達, 大崎往夫, 中島収

肝臓　47　(12)　574-581　2006年12月25日
出版者・発行元：一般社団法人日本肝臓学会
DOI： 10.2957/kanzo.47.574 　

ISSN： 0451-4203

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症例は21歳男性．腎炎の経過観察中に，USにて低エコー，単純CTにて高吸収を呈し，dynamic CTおよびMRIにて早期相で造影される多発結節を認めた．レボビスト造影USのpost vascular imageやSPIO MRIでは，Kuppfer細胞の存在を示唆され，USガイド下針生検では，FNH様過形成結節と診断されたが，single level dynamic CTHAにてリング様濃染を結節様高吸収域内部に認めた．周辺肝が脂肪肝を呈したため，結節血流流出部がspared areaとなり，リング様濃染部に相当する領域を含めて画像上結節様に観察されていたと考えられた．過形成結節においても，肝細胞癌に特徴的とされるリング様濃染を呈することがあると考えられ報告した．<br>
リピオドール使用の現状とTAEにおける功罪 1.リピオドールの肝動脈内投与の肝機能に与える影響についての検討―単独,乳化剤,TAEでの比較検討―

木村達, 大崎往夫, 喜多竜一, 西川浩樹, 那須章洋, 池田敦之, 中辻正人, 齋藤澄夫, 西島規浩, 波多野貴昭, 松尾裕央, 川上尚人, 坂本康明

IVR　21　(4)　429-435　2006年10月1日

ISSN： 1340-4520
RFA施行時におけるMulti‐phase Real‐time Virtual Sonographyの有用性

西島規浩, 大崎往夫, 川上尚人, 坂本康明, 松尾裕央, 斉藤澄夫, 波多野貴昭, 池田敦之, 那須章洋, 西川浩樹, 大鶴繁, 辻賢太郎, 津村剛彦, 喜多竜一, 圓尾隆典, 木村達

肝臓　47　(Supplement 2)　A455　2006年9月5日

ISSN： 0451-4203

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共同研究・競争的資金等の研究課題 7

抗がん薬ナノ粒子の極微小化と薬物動態の解明

笠井均, 川上尚人, 雲林院宏

2026年4月1日～ 2030年3月31日
自己抗体同定法の確立と新規自己抗体の同定様式

2024年4月～ 2029年3月
KEAP1-NRF2変異を有する標準治療不応または不耐の固形腫瘍に対するマイトマイシンC単剤療法の有効性および安全性を検討する第II相試験

川上尚人

2026年4月～ 2027年3月
CT画像、病理組織、臨床情報からMSI-H胃癌を同定するAIアルゴリズムの構築

川上尚人

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Kindai University

2022年4月～ 2026年3月
Stage II/III胃癌に対するTS-1術後補助化学療法とMSI/dMMR

川上尚人

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

研究種目：Grant-in-Aid for Early-Career Scientists

研究機関：Kindai University

2018年4月1日～ 2022年3月31日

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現在、stage II/III胃癌に対してはS-1単独療法が本邦における標準治療である。MAGIC trialの付随研究の結果は、S-1単剤による術後補助化学療法によってむしろ生存期間が短縮する症例が一定数存在する可能性を示唆している。本研究によって、MSI/dMMRとS-1単剤による術後補助化学療法の効果との関連が明らかとなれば、現在、米国のstage II 大腸癌に対して行われているのと同じ戦略、つまりMSI-Hであれば術後補助化学療法を行わないといった方針を選ぶことが可能になる。現在までに100例のMSI解析が終了し、16例のPCR不能例があったものの10例でMSI-Hを確認している。さらに2020年4月中に110例程度解析追加見込みで、全体で2100程度、その中から20例程度のMSI-Hが見込まれる。 100例のpreliminaryなデータでは、全体の無再発生存期間については既報のACTS-GC試験とほぼ同様であり患者背景に問題がないことが確認できている。一方でMSI-H vs. MSSに予後およびS-1治療による再発抑制効果に有意差は認められなかった。近年MSI statusと切除可能胃癌の予後との関係を示すデータが相次いで報告されているが、stage IIにおいてはMSI statusが化学療法の効果を妨げない、つまり無増悪生存期間も全生存期間も同等とするものが多い。無造悪生存期間については我々の結果も同様であったが、全生存はMSI-HがMSSより有意に良好であり、その原因についての考察のため、下記別項のような追加の検討を予定している。
３学会合同「がんゲノムネット」を用いた国民に対する「がんゲノム医療」に係る教育と正しい情報伝達に関する研究

2018年4月～ 2021年3月
ＭＥＴ遺伝子増幅胃癌におけるＭＥＴチロシンキナーゼ阻害剤の抗腫瘍効果の解析

岡本渉, 中川和彦, 西尾和人, 岡本勇, 荒尾徳三, 川上尚人

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

研究種目：Grant-in-Aid for Scientific Research (C)

2012年4月1日～ 2015年3月31日

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MET遺伝子増幅をもつ胃癌細胞は、METチロシンキナーゼ阻害剤（MET阻害剤）の暴露により、アポトーシスをおこすことで著明な抗腫瘍効果を示す。本研究は、MET阻害剤により引き起こされるアポトーシスの分子メカニズムを明らかにした。また、患者検体から得られた組織標本を用いて、日本人の胃癌におけるMET遺伝子増幅の頻度や予後などの疫学情報を明らかにした。さらに、MET阻害剤が臨床応用された後に問題となることが想定される、薬剤耐性のメカニズムを解析するために重要なMET阻害剤耐性の胃癌細胞株を樹立した。

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