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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References
Baba H, Watanabe M, Okabe H et al (2012) Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer. Br J Cancer 107:1950–1955
Brookmeyer R, Crowley J (1982) A confidence interval for the median survival time. Biometrics 38:29–41
Fuse N, Doi T, Ohtsu A et al (2008) Safety of irinotecan and infusional fluorouracil/leucovorin (FOLFIRI) in Japan: a retrospective review of 48 patients with metastatic colorectal cancer. Int J Clin Oncol 13:144–149
Goto A, Yamada Y, Yasui H et al (2006) Phase II study of combination therapy with S-1 and irinotecan in patients with advanced colorectal cancer. Ann Oncol 17:968–973
Komatsu Y, Yuki S, Fuse N et al (2010) Phase 1/2 clinical study of irinotecan and oral S-1 (IRIS) in patients with advanced gastric cancer. Adv Ther 27:483–492
Komatsu Y, Yuki S, Sogabe S et al (2011) Phase II study of combined treatment with irinotecan and S-1 (IRIS) in patients with inoperable or recurrent advanced colorectal cancer (HGCSG0302). Oncology 80:70–75
Muro K, Boku N, Shimada Y et al (2010) Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol 11:853–860
National Comprehensive Cancer Network (2014a) NCCN Clinical Practice Guidelines in Oncology: Colon Cancer, version 3.2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed May 20 2014
National Comprehensive Cancer Network (2014b) NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer, version 3.2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed May 20 2014
O’Neil BH, Goldberg RM (2008) Innovations in chemotherapy for metastatic colorectal cancer: an update of recent clinical trials. The Oncol 13:1074–1083
Peeters M, Price TJ, Cervantes A et al (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28:4706–4713
Schmoll HJ, Van Cutsem E, Stein A et al (2012) ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol 23:2479–2516
Shiozawa M, Akaike M, Sugano N et al (2010) A phase II study of combination therapy with irinotecan and S-1 (IRIS) in patients with advanced colorectal cancer. Cancer Chemother Pharmacol 66:987–992
Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311–2319
Spiegelhalter DJ, Freedman LS, Parmar MKB (1994) Bayesian approaches to randomized trials. J R Stat Soc 157:357–387
Tournigand C, André T, Achille E et al (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22:229–237
Tsunoda A, Yasuda N, Nakao K et al (2009) Phase II study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer. Oncology 77:192–196
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.
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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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DOI: https://doi.org/10.1007/s00432-014-1783-3