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Phase II trial of an alternating regimen consisting of first-line mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: FIREFOX plus bevacizumab trial (KSCC0801)

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Abstract

Objectives

The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer.

Methods

Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival.

Results

The median age was 60 years (range 37–75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6–16.3) and median overall survival was 28.4 months (95 % CI 22.6–39.1). The overall response rate was 60.0 % (95 % CI 45.2–73.6). Regarding toxicity, the commonest grade 3–4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3–4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3–4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %).

Conclusions

An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

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References

  1. Jemal A, Tiwari RC, Murray T et al (2004) Cancer statistics, 2004. CA Cancer J Clin 54:8–29

    Article  PubMed  Google Scholar 

  2. Parkin DM (2001) Global cancer statistics in the year 2000. Lancet Oncol 2:533–543

    Article  CAS  PubMed  Google Scholar 

  3. Fuchs CS, Marshall J, Mitchell E et al (2007) Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study. J Clin Oncol 25:4779–4786

    Article  CAS  PubMed  Google Scholar 

  4. Tournigand C, Andre 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

    Article  CAS  PubMed  Google Scholar 

  5. Cassidy J, Clarke S, Diaz-Rubio E et al (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26:2006–2012

    Article  CAS  PubMed  Google Scholar 

  6. Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  CAS  PubMed  Google Scholar 

  7. Van Cutsem E, Kohne CH, Hitre E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417

    Article  PubMed  Google Scholar 

  8. Grothey A, Sargent D, Goldberg RM et al (2004) Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 22:1209–1214

    Article  CAS  PubMed  Google Scholar 

  9. Grothey A, Sargent D (2005) Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line. J Clin Oncol 23:9441–9442

    Article  PubMed  Google Scholar 

  10. Falcone A, Ricci S, Brunetti I et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25:1670–1676

    Article  CAS  PubMed  Google Scholar 

  11. Souglakos J, Androulakis N, Syrigos K et al (2006) FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 94:798–805

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Masi G, Loupakis F, Salvatore L et al (2010) Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol 11:845–852

    Article  CAS  PubMed  Google Scholar 

  13. Montagnani F, Chiriatti A, Turrisi G et al (2011) A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity. Colorectal Dis 13:846–852

    Article  CAS  PubMed  Google Scholar 

  14. Oki E, Emi Y, Akagi Y et al (2013) Phase II trial of alternating mFOLFOX6 and FOLFIRI regimens in the first-line treatment for unresectable or metastatic colorectal cancer (KSCC0701). Oncology 84:233–239

    Article  CAS  PubMed  Google Scholar 

  15. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  CAS  PubMed  Google Scholar 

  16. Horita Y, Yamada Y, Kato K et al (2012) Phase II clinical trial of second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: AVASIRI trial. Int J Clin Oncol 17:604–609

    Article  CAS  PubMed  Google Scholar 

  17. Bennouna J, Sastre J, Arnold D et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37

    Article  CAS  PubMed  Google Scholar 

  18. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  19. Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181

    Article  PubMed  Google Scholar 

  20. Tournigand C, Cervantes A, Figer A et al (2006) OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer—a GERCOR study. J Clin Oncol 24:394–400

    Article  CAS  PubMed  Google Scholar 

  21. Vaidyanathan G, Groman A, Wilding G et al (2010) Stop and go FOLFOX plus bevacizumab chemotherapy in the first-line treatment of metastatic colorectal cancer. Oncology 79:67–71

    Article  CAS  PubMed  Google Scholar 

  22. Aparicio J, Fernandez-Martos C, Vincent JM et al (2005) FOLFOX alternated with FOLFIRI as first-line chemotherapy for metastatic colorectal cancer. Clin Colorectal Cancer 5:263–267

    Article  CAS  PubMed  Google Scholar 

  23. Hebbar M, Tournigand C, Lledo G et al (2006) Phase II trial alternating FOLFOX-6 and FOLFIRI regimens in second-line therapy of patients with metastatic colorectal cancer (FIREFOX study). Cancer Invest 24:154–159

    Article  CAS  PubMed  Google Scholar 

  24. Heinemann V, von Weikersthal LF, Decker T et al (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 15:1065–1075

    Article  CAS  PubMed  Google Scholar 

  25. Yamada Y, Takahari D, Matsumoto H et al (2013) Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus s-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 14:1278–1286

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all the patients and families who participated in this trial, and we are indebted to the physicians and all of the clinical study teams at the participating institutions. We also thank Ms. Sanae Sakamoto for her excellent secretarial assistance at the data center of Clinical Research Support Center Kyushu.

Conflict of interest

The authors declare that they have no conflict of interest. All co-authors have seen and agree with the contents of the manuscript, and there are no financial interests to report. We certify that the submission presents original work and is not under review by any other publications.

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Authors and Affiliations

  1. Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan

    Keisuke Miwa

  2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Eiji Oki, Hiroshi Saeki & Yoshihiko Maehara

  3. Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan

    Yasunori Emi

  4. Department of Gastroenterological Surgery/Clinical Research Institute Cancer Research Division, National Kyushu Medical Center, Fukuoka, Japan

    Tetsuya Kusumoto

  5. Department of Surgery, Kurume University School of Medicine, Kurume, Japan

    Yoshito Akagi

  6. Department of Surgery, Kurume University Medical Center, Kurume, Japan

    Yutaka Ogata

  7. Department of Surgery I, Ryukyu University, Okinawa, Japan

    Hironori Samura

  8. Medical Information Center, Kyushu University Hospital, Fukuoka, Japan

    Shoji Tokunaga

  9. Department of Surgery, Sasebo City General Hospital, Sasebo, Japan

    Hiroshi Ishikawa

  10. Department of Surgery, Social Insurance Tagawa Hospital, Tagawa, Japan

    Takaho Tanaka

  11. Department of Surgery, Omuta City Hospital, Omuta, Japan

    Susumu Sueyoshi

  12. Department of Surgery, Steel Memorial Yawata Hospital, Kitakyushu, Japan

    Hidefumi Higashi

  13. Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan

    Hiroyuki Matsuda

  14. Department of Surgery, Nakagami Hospital, Okinawa, Japan

    Tetsuo Touyama

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  1. Keisuke Miwa
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  2. Eiji Oki
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  14. Hiroyuki Matsuda
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  15. Tetsuo Touyama
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  16. Yoshihiko Maehara
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Kyushu Study Group of Clinical Cancer

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Correspondence to Keisuke Miwa.

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Miwa, K., Oki, E., Emi, Y. et al. Phase II trial of an alternating regimen consisting of first-line mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: FIREFOX plus bevacizumab trial (KSCC0801). Int J Clin Oncol 21, 110–117 (2016). https://doi.org/10.1007/s10147-015-0850-3

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  • DOI: https://doi.org/10.1007/s10147-015-0850-3

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