Advertisement

Journal of Cancer Research and Clinical Oncology

, Volume 141, Issue 1, pp 153–160 | Cite as

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

  • Hirofumi YasuiEmail author
  • Kei Muro
  • Yasuhiro Shimada
  • Akihito Tsuji
  • Shinichi Sameshima
  • Hideo Baba
  • Taroh Satoh
  • Tadamichi Denda
  • Kenji Ina
  • Tomohiro Nishina
  • Kensei Yamaguchi
  • Taito Esaki
  • Shinya Tokunaga
  • Hiroyuki Kuwano
  • Narikazu Boku
  • Yoshito Komatsu
  • Masahiko Watanabe
  • Ichinosuke Hyodo
  • Satoshi Morita
  • Kenichi Sugihara
Original Article – Clinical Oncology

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).

Keywords

Colorectal cancer FIRIS Irinotecan IRIS S-1 

Notes

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.

References

  1. 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 107:1950–1955PubMedCentralPubMedCrossRefGoogle Scholar
  2. Brookmeyer R, Crowley J (1982) A confidence interval for the median survival time. Biometrics 38:29–41CrossRefGoogle Scholar
  3. 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 13:144–149PubMedCrossRefGoogle Scholar
  4. 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 17:968–973PubMedCrossRefGoogle Scholar
  5. 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 27:483–492PubMedCrossRefGoogle Scholar
  6. 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 80:70–75PubMedCrossRefGoogle Scholar
  7. 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 11:853–860PubMedCrossRefGoogle Scholar
  8. 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
  9. 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
  10. O’Neil BH, Goldberg RM (2008) Innovations in chemotherapy for metastatic colorectal cancer: an update of recent clinical trials. The Oncol 13:1074–1083CrossRefGoogle Scholar
  11. 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 28:4706–4713PubMedCrossRefGoogle Scholar
  12. 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 23:2479–2516PubMedCrossRefGoogle Scholar
  13. 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 66:987–992PubMedCrossRefGoogle Scholar
  14. 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 26:2311–2319PubMedCrossRefGoogle Scholar
  15. Spiegelhalter DJ, Freedman LS, Parmar MKB (1994) Bayesian approaches to randomized trials. J R Stat Soc 157:357–387CrossRefGoogle Scholar
  16. 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 22:229–237PubMedCrossRefGoogle Scholar
  17. 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 77:192–196PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hirofumi Yasui
    • 1
    Email author
  • Kei Muro
    • 2
  • Yasuhiro Shimada
    • 3
  • Akihito Tsuji
    • 4
  • Shinichi Sameshima
    • 5
  • Hideo Baba
    • 6
  • Taroh Satoh
    • 7
  • Tadamichi Denda
    • 8
  • Kenji Ina
    • 9
  • Tomohiro Nishina
    • 10
  • Kensei Yamaguchi
    • 11
  • Taito Esaki
    • 12
  • Shinya Tokunaga
    • 13
  • Hiroyuki Kuwano
    • 14
  • Narikazu Boku
    • 15
  • Yoshito Komatsu
    • 16
  • Masahiko Watanabe
    • 17
  • Ichinosuke Hyodo
    • 18
  • Satoshi Morita
    • 19
  • Kenichi Sugihara
    • 20
  1. 1.Division of Gastrointestinal OncologyShizuoka Cancer CenterShizuokaJapan
  2. 2.Department of Clinical OncologyAichi Cancer Center HospitalNagoyaJapan
  3. 3.Division of Gastrointestinal OncologyNational Cancer Center HospitalTokyoJapan
  4. 4.Department of Medical OncologyKobe City Medical Center General HospitalKobeJapan
  5. 5.Department of SurgeryDokkyo Medical University Koshigaya HospitalKoshigayaJapan
  6. 6.Department of Gastroenterological Surgery, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
  7. 7.Department of Frontier Science for Cancer and ChemotherapyOsaka University Graduate School of MedicineSuitaJapan
  8. 8.Department of GastroenterologyChiba Cancer CenterChibaJapan
  9. 9.Department of Medical OncologyNagoya Memorial HospitalNagoyaJapan
  10. 10.Department of Medical OncologyNational Hospital Organization Shikoku Cancer CenterMatsuyamaJapan
  11. 11.Department of GastroenterologySaitama Cancer CenterSaitamaJapan
  12. 12.Department of Gastrointestinal and Medical OncologyNational Kyushu Cancer CenterFukuokaJapan
  13. 13.Department of Clinical OncologyOsaka City General HospitalOsakaJapan
  14. 14.Department of General Surgical Science, Graduate School of MedicineGunma UniversityMaebashiJapan
  15. 15.Department of Clinical OncologySt. Marianna University School of MedicineKawasakiJapan
  16. 16.Department of Cancer ChemotherapyHokkaido University Hospital Cancer CenterSapporoJapan
  17. 17.Department of SurgeryKitasato University School of MedicineSagamiharaJapan
  18. 18.Division of GastroenterologyTsukuba University HospitalTsukubaJapan
  19. 19.Department of Biostatistics and EpidemiologyYokohama City University Medical CenterYokohamaJapan
  20. 20.Department of Surgical OncologyTokyo Medical and Dental University Graduate SchoolTokyoJapan

Personalised recommendations