S-1 and irinotecan with or without bevacizumab versus 5-fluorouracil and leucovorin plus oxaliplatin with or without bevacizumab in metastatic colorectal cancer: a pooled analysis of four phase II studies
S-1, a novel oral prodrug of 5-fluorouracil (5-FU), and irinotecan with or without bevacizumab is known to be effective in metastatic colorectal cancer (mCRC). However, it is not clear whether S-1 and irinotecan confers benefits compared to 5-FU and leucovorin plus oxaliplatin (FOLFOX) in patients with mCRC. Our aim was to compare the efficacy and safety of these regimens.
We analyzed 187 patients with previously untreated mCRC who were enrolled in four phase II studies: SIR (S-1 and irinotecan, n = 40), SIRB (S-1 and irinotecan with bevacizumab, n = 51), FOLFOX (5-FU and leucovorin plus oxaliplatin, n = 46), and STOX (stop-and-go strategy of modified FOLFOX-6 with bevacizumab, n = 50). We evaluated efficacy and safety between SIR/SIRB and FOLFOX/STOX.
Baseline characteristics were similar in the two groups composed of SIR/SIRB (n = 91) and FOLFOX/STOX (n = 96). The overall response rates were not significantly different between the two groups (65 % in SIR/SIRB vs. 52 % in FOLFOX/STOX, p = 0.125). The median progression-free survival was 10.9 months in SIR/SIRB versus 12.1 months in FOLFOX/STOX (p = 0.59). The median overall survival was 27.3 months in SIR/SIRB versus 26.8 months in FOLFOX/STOX (p = 0.97). Gastrointestinal adverse events were the most common toxicities in SIR/SIRB, while neutropenia and sensory neuropathy were the most common toxicities in FOLFOX/STOX.
S-1 and irinotecan with or without bevacizumab was well tolerated and showed similar response rates and survival compared to the FOLFOX regimen. This combination should be considered as an experimental first-line treatment for mCRC.
KeywordsColorectal cancer Irinotecan Phase II Pooled analysis S-1
Compliance with ethical standards
This work was supported in part by Taiho Pharmaceutical Co., Ltd. Tatsuro Yamaguchi has received speakers’ bureau from Taiho and Yakult. Yasushi Ichikawa has received research funding from Taiho and Yakult. Ayumu Goto has received honoraria from Taiho. Hisateru Yasui has received honoraria from Taiho and owns stock in Yakult. Yasuhiro Shimada has received honoraria from Taiho and Yakult, and research funding from Taiho and Yakult and has consulting fees from Taiho. Yasuhide Yamada has received honoraria from Taiho and Yakult, and research funding from Taiho and Daiichi-Sankyo. All other authors declare that they have no conflict of interest relevant to this study. All procedures performed in phase II studies were in accordance with the ethical standards of the institutional review board at each participating center and with the 1964 Declaration of Helsinki and Japanese Good Clinical Practice Guidelines.
Written informed consent was obtained from all individual participants included in each phase II study.
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