A phase II trial of capecitabine plus cisplatin (XP) for patients with advanced gastric cancer with early relapse after S-1 adjuvant therapy: XParTS-I trial
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In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294).
HER2-negative gastric cancer patients treated with adjuvant chemotherapy including S-1 for more than 12 weeks and relapsed within 6 months were treated with capecitabine 1000 mg/m2 bid for 14 days plus cisplatin 80 mg/m2 on day 1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety.
Forty patients (median age 64) were enrolled; of those, 37 (92.5%) received adjuvant S-1 monotherapy. Median PFS was 4.4 months (95% CI 3.6–5.1), which was longer than the 2-month protocol-specified threshold (p < 0.001). Median OS was 13.7 months (95% CI 9.0–17.7) and ORR was 8/30 (26.7%) (95% CI 14.2–44.4). Most common grade ≥ 3 adverse events were neutropenia (23%), anemia (18%), elevated serum creatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%).
XP was safe and effective in patients with early relapse after S-1 adjuvant chemotherapy for curatively resected gastric cancers. XP may be a good option for the treatment of patients after early failure after adjuvant S-1.
KeywordsAdvanced gastric cancer Capecitabine plus cisplatin (XP) S-1 adjuvant therapy Early relapse Fluoropyrimidine switching
We thank the investigators from the following institutions who enrolled patients for this trial: Osaka General Medical Center, Yokohama Municipal Citizen’s Hospital, Hiroshima University Graduate School of Medicine, Saitama Cancer Center, Yokohama City University, Yamaguchi University Graduate School of Medicine, Kochi Medical School, Kanagawa Cancer Center, Yokohama City University, Kobe City Medical Center General Hospital, Osaka City General Hospital, Sakai Municipal Hospital, Nagoya University Graduate School of Medicine, Oita University Faculty of Medicine, Hiroshima City Asa Hospital, and Niigata Cancer Center Hospital. Furthermore, we deeply appreciate all patients who participated in the trial. We acknowledge Dr Mark Abramovitz of Edanz Medical Writing for editorial support, which was funded by the non-profit organization Epidemiological and Clinical Research Information Network (ECRIN).
This work was supported by the non-profit organization Epidemiological and Clinical Research Information Network (ECRIN).
Compliance with ethical standards
Conflict of interest
The individual conflict of interest disclosure is as follows: K. Nishikawa has received honoraria from Chugai, Taiho, Yakult, Eli Lilly, Tsumura, and EA Pharma, and research funding from Yakult and Taiho, outside the submitted work. T. Yoshikawa has received lecture fees from Chugai, Taiho, Yakult, Eli Lilly and Ono, and for advisory work from Ono and MSD, outside the submitted work. K. Yamaguchi has received personal fees from Chugai, Taiho, Yakult, Takeda, Merck and Eli Lilly, and research funding from MSD, Merck, Bristol, Ono, Dainippon Sumitomo, Taiho, Daiichi-Sankyo and Yakult, outside the submitted work. S. Yoshino has received honoraria from Chugai, Taiho, Ono and Eli Lilly, outside the submitted work. Y. Kodera has received research funding from Chugai, Taiho, Daiichi-Sankyo, Bristol-Myers, Eli Lilly, Otsuka, Takeda, Yakult, CSL Behring, Pfizer, Ono, Kaken, Tsumura, EA Pharma, Novartis, KCI and the Japan Blood Products Organization, outside the submitted work. S. Morita has received honoraria from Chugai and Taiho, outside the submitted work. J. Sakamoto has received consultant fee from Takeda, and Honoraria from Tsumura and Chugai, outside the submitted work. None of the remaining authors have potential conflicts of interest to declare.
This trial was conducted in compliance with the ethical principles of the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies of the Japanese Ministry of Health, Labour and Welfare. This trial was approved by the institutional review boards or ethics committees at all participating centers. This trial was registered with ClinicalTrials.gov (NCT01412294).
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