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A phase 3 non-inferiority study of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer: updated results of the FIRIS study

  • Original Article – Clinical Oncology
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Abstract

Purpose

The FIRIS study previously demonstrated non-inferiority of IRIS (irinotecan plus S-1) to FOLFIRI (5-fluorouracil/leucovorin with irinotecan) for progression-free survival as the second-line chemotherapy for metastatic colorectal cancer (mCRC) as the primary endpoint. The overall survival (OS) data were immature at the time of the primary analysis.

Methods

Between 30 January 2006 and 29 January 2008, 426 patients with mCRC who failed in first-line chemotherapy were randomly assigned to receive either FOLFIRI or IRIS. After the primary analysis, the follow-up survey was cut off on 29 July 2010, and the final OS data were analysed.

Results

With a median follow-up of 39.2 months, the median OS was 17.4 months in the FOLFIRI group and 17.8 months in the IRIS group [hazard ratio (HR) 0.900; 95 % confidence interval (CI) 0.728–1.112]. In the pre-planned subgroup of patients who received prior chemotherapy containing oxaliplatin, the median OS was 12.7 months in the FOLFIRI group and 15.3 months in the IRIS group (HR 0.755; 95 % CI 0.580–0.983).

Conclusions

IRIS is non-inferior to FOLFIRI for OS as second-line chemotherapy for mCRC. IRIS can be an option for second-line chemotherapy of mCRC. (ClinicalTrials.gov Number: NCT00284258).

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Acknowledgments

We thank all of the patients, their families, and the institutions involved in this study (see “Appendix”). The authors also thank Yuh Sakata, Yasuo Ohashi, and Nobuyuki Yamamoto for the Independent Data Monitoring Committee, and Atsushi Ohtsu, Yasuaki Arai, and Junji Tanaka for the Independent Central Review Committee for their contributions to this report. The authors dedicate this article to the memory of Prof. Hiroya Takiuchi, who contributed to the conception and design of this study. The senior academic authors designed the trial in cooperation with the study sponsors. The sponsors provided funding and organisational support, collected data, and performed analyses, but did not undertake any data interpretation. This report was written by the corresponding author (with additional input from the other authors), who had unrestricted access to the raw study data, gives assurance for the accuracy and completeness of the reported analyses, and had final responsibility for the decision to submit for publication. This work was funded by Taiho Pharmaceutical Co. Ltd., Japan, and Daiichi Sankyo Co. Ltd., Japan.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

Authors

Corresponding author

Correspondence to Hirofumi Yasui.

Appendix (participating institutes): FIRIS Study Group

Appendix (participating institutes): FIRIS Study Group

List of participating institutions in order of patient recruitment:

Shizuoka Cancer Center (Shizuoka, Japan); Aichi Cancer Center Hospital (Nagoya, Japan); National Cancer Center Hospital (Tokyo, Japan); Kochi Health Sciences Center (Kochi, Japan); Gunma Prefectural Cancer Center (Gunma, Japan); Kumamoto University Hospital (Kumamoto, Japan); Kinki University School of Medicine (Osaka, Japan); Chiba Cancer Center (Chiba, Japan); Nagoya Memorial Hospital (Nagoya, Japan); National Hospital Organization Shikoku Cancer Center (Matsuyama, Japan); Saitama Cancer Center (Saitama, Japan); Osaka Medical College Hospital (Takatsuki, Japan); National Kyushu Cancer Center (Fukuoka, Japan); Osaka City General Hospital (Osaka, Japan); Gunma University Graduate School of Medicine (Maebashi, Japan); Hokkaido University Hospital Cancer Center (Sapporo, Japan); National Hospital Organization Kyoto Medical Center (Kyoto, Japan); Keio University Hospital (Tokyo, Japan); Kansai Rosai Hospital (Hyogo, Japan); Tokyo Medical and Dental University (Tokyo, Japan); Osaka Medical Center for Cancer and Cardiovascular Diseases (Osaka, Japan); Aomori Prefectural Central Hospital (Aomori, Japan); Showa University Toyosu Hospital (Tokyo, Japan); Minoh City Hospital (Osaka, Japan); Saiseikai Kumamoto Hospital (Kumamoto, Japan); Toyama University Hospital (Toyama, Japan); National Hospital Organization Kagoshima Medical Center (Kagoshima, Japan); Tonan Hospital (Sapporo, Japan); Kanagawa Cancer Center (Yokohama, Japan); Niigata Cancer Center Hospital (Niigata, Japan); Saku Central Hospital (Nagano, Japan); Hyogo Cancer Center (Hyogo, Japan); Hiroshima University Hospital (Hiroshima, Japan); Tomakomai Nissho Hospital (Hokkaido, Japan); Aichi Cancer Center Aichi Hospital (Aichi, Japan); National Hospital Organization Nagoya Medical Center (Nagoya, Japan); Kobe University Hospital (Kobe, Japan); Yamagata Prefectural Central Hospital (Yamagata, Japan); Yokohama City University Hospital (Yokohama, Japan); and Kitasato University East Hospital (Kanagawa, Japan).

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Yasui, H., Muro, K., Shimada, Y. et al. A phase 3 non-inferiority study of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer: updated results of the FIRIS study. J Cancer Res Clin Oncol 141, 153–160 (2015). https://doi.org/10.1007/s00432-014-1783-3

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