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

Author:

Falcone Alfredo1,Ricci Sergio1,Brunetti Isa1,Pfanner Elisabetta1,Allegrini Giacomo1,Barbara Cecilia1,Crinò Lucio1,Benedetti Giovanni1,Evangelista Walter1,Fanchini Laura1,Cortesi Enrico1,Picone Vincenzo1,Vitello Stefano1,Chiara Silvana1,Granetto Cristina1,Porcile Gianfranco1,Fioretto Luisa1,Orlandini Cinzia1,Andreuccetti Michele1,Masi Gianluca1

Affiliation:

1. From the U.O. Oncologia Medica, Istituto Toscano Tumori, Livorno; S.C. di Oncologia Medica, Ospedale S. Maria della Misericordia, Perugia; U.O. Oncologia Medica, Ospedale di Macerata, Macerata; Centro Oncologico ed Ematologico Subalpino, ASO Ospedale S. Giovanni Battista Le Molinette, Torino; Dipartimento di Medicina Sperimentale e Patologia, Oncologia Medica, Università la Sapienza, Roma; U.O. Oncologia Medica, Ospedale S. Elia, Caltanissetta; Istituto Nazionale per la Ricerca sul Cancro, Genova; S.C....

Abstract

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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