TY - JOUR
T1 - Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer
T2 - a randomised phase 3 study
AU - Boku, Narikazu
AU - Yamamoto, Seiichiro
AU - Fukuda, Haruhiko
AU - Shirao, Kuniaki
AU - Doi, Toshihiko
AU - Sawaki, Akira
AU - Koizumi, Wasaburo
AU - Saito, Hiroshi
AU - Yamaguchi, Kensei
AU - Takiuchi, Hiroya
AU - Nasu, Junichiro
AU - Ohtsu, Atsushi
N1 - Funding Information:
We thank A Kimura and N Murata for data management; N Ishizuka, K Yoshimura, and A Kuchiba for statistical analyses; K Nakamura for editorial assistance; and the data and safety monitoring and audit committees of JCOG. This study was supported mainly by grants-in-aid for cancer research ( 11S-3, 11S-4, 14S-3, 14S-4, 17S-3, 17S-5 ) from the Ministry of Health, Labour and Welfare of Japan , and partly by contracts for providing safety data to Taiho Pharmaceutical and Yakult Honsha.
PY - 2009/11
Y1 - 2009/11
N2 - Background: The best chemotherapy regimen for metastatic gastric cancer is uncertain, but promising findings have been reported with irinotecan plus cisplatin and S-1 (tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate). We aimed to investigate the superiority of irinotecan plus cisplatin and non-inferiority of S-1 compared with fluorouracil, with respect to overall survival, in patients with metastatic gastric cancer. Methods: We undertook a phase 3 open label randomised trial in 34 institutions in Japan. We enrolled patients aged 20-75 years or younger, who had histologically proven gastric adenocarcinoma, and randomly assigned them by minimisation to receive either: a continuous infusion of fluorouracil (800 mg/m2 per day, on days 1-5) every 4 weeks (n=234); intravenous irinotecan (70 mg/m2, on days 1 and 15) and cisplatin (80 mg/m2, on day 1) every 4 weeks (n=236); or oral S-1 (40 mg/m2, twice a day, on days 1-28) every 6 weeks (n=234). The primary endpoint was overall survival. Analyses were done by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00142350, and with UMIN-CTR, number C000000062. Findings: All randomised patients were included in the primary analysis. Median overall survival was 10·8 months (IQR 5·7-17·8) for individuals assigned fluorouracil, 12·3 months (8·1-19·5) for those allocated irinotecan plus cisplatin (hazard ratio 0·85 [95% CI 0·70-1·04]; p=0·0552), and 11·4 months (6·4-21·3) for those assigned S-1 (0·83 [0·68-1·01]; p=0·0005 for non-inferiority). Three treatment-related deaths occurred in the irinotecan plus cisplatin group and one was recorded in the S-1 group. Interpretation: S-1 is non-inferior to fluorouracil and, in view of the convenience of an oral administration, could replace intravenous fluorouracil for treatment of unresectable or recurrent gastric cancer, at least in Asia. Irinotecan plus cisplatin is not superior to fluorouracil in this setting. Funding: Ministry of Health, Labour, and Welfare of Japan; Taiho Pharmaceutical; Yakult Honsha.
AB - Background: The best chemotherapy regimen for metastatic gastric cancer is uncertain, but promising findings have been reported with irinotecan plus cisplatin and S-1 (tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate). We aimed to investigate the superiority of irinotecan plus cisplatin and non-inferiority of S-1 compared with fluorouracil, with respect to overall survival, in patients with metastatic gastric cancer. Methods: We undertook a phase 3 open label randomised trial in 34 institutions in Japan. We enrolled patients aged 20-75 years or younger, who had histologically proven gastric adenocarcinoma, and randomly assigned them by minimisation to receive either: a continuous infusion of fluorouracil (800 mg/m2 per day, on days 1-5) every 4 weeks (n=234); intravenous irinotecan (70 mg/m2, on days 1 and 15) and cisplatin (80 mg/m2, on day 1) every 4 weeks (n=236); or oral S-1 (40 mg/m2, twice a day, on days 1-28) every 6 weeks (n=234). The primary endpoint was overall survival. Analyses were done by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00142350, and with UMIN-CTR, number C000000062. Findings: All randomised patients were included in the primary analysis. Median overall survival was 10·8 months (IQR 5·7-17·8) for individuals assigned fluorouracil, 12·3 months (8·1-19·5) for those allocated irinotecan plus cisplatin (hazard ratio 0·85 [95% CI 0·70-1·04]; p=0·0552), and 11·4 months (6·4-21·3) for those assigned S-1 (0·83 [0·68-1·01]; p=0·0005 for non-inferiority). Three treatment-related deaths occurred in the irinotecan plus cisplatin group and one was recorded in the S-1 group. Interpretation: S-1 is non-inferior to fluorouracil and, in view of the convenience of an oral administration, could replace intravenous fluorouracil for treatment of unresectable or recurrent gastric cancer, at least in Asia. Irinotecan plus cisplatin is not superior to fluorouracil in this setting. Funding: Ministry of Health, Labour, and Welfare of Japan; Taiho Pharmaceutical; Yakult Honsha.
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U2 - 10.1016/S1470-2045(09)70259-1
DO - 10.1016/S1470-2045(09)70259-1
M3 - Article
C2 - 19818685
AN - SCOPUS:71249128928
SN - 1470-2045
VL - 10
SP - 1063
EP - 1069
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 11
ER -
