Journal of Clinical Oncology, Vol 25, No 13 (May 1), 2007: pp. 1670-1676
© 2007 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2006.09.0928
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
Alfredo Falcone,
Sergio Ricci,
Isa Brunetti,
Elisabetta Pfanner,
Giacomo Allegrini,
Cecilia Barbara,
Lucio Crinò,
Giovanni Benedetti,
Walter Evangelista,
Laura Fanchini,
Enrico Cortesi,
Vincenzo Picone,
Stefano Vitello,
Silvana Chiara,
Cristina Granetto,
Gianfranco Porcile,
Luisa Fioretto,
Cinzia Orlandini,
Michele Andreuccetti,
Gianluca Masi
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. di Oncologia, Azienda Ospedaliera S. Croce e Carle, Cuneo; Oncologia Medica, P.O. S. Lazzaro, Alba; Oncologia Medica, Ospedale S. Maria Annunziata, Istituto Toscano Tumori, Firenze, Italy; U.O. Oncologia Medica, Azienda Ospedaliero-Universitaria, Istituto Toscano Tumori; and Dipartimento di Oncologia, dei Trapianti e Nuove Tecnologie in Medicina, Università degli Studi, Pisa, Italy
Address reprint requests to Alfredo Falcone, MD, Cattedra di Oncologia Medica, University of Pisa, Department of Oncology, Azienda USL-6 of Livorno, Viale Alfieri, 36, 57124 Livorno, Italy; e-mail: a.falcone{at}med.unipi.it
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.
Supported in part by a research grant of the Associazione Italiana Ricerca Cancro (A.I.R.C.) and by the Fondazione A.R.C.O.
Presented at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006, and at the American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, San Francisco, CA, January 24-27, 2006.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike Complore Connotea Del.icio.us Digg Facebook Reddit Technorati Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
B. Nordlinger, E. Van Cutsem, T. Gruenberger, B. Glimelius, G. Poston, P. Rougier, A. Sobrero, M. Ychou, and on behalf of the European Colorectal Metastases Tr
Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel
Ann. Onc.,
June 1, 2009;
20(6):
985 - 992.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Aranda, M. Valladares, M. Martinez-Villacampa, M. Benavides, A. Gomez, B. Massutti, E. Marcuello, M. Constenla, J. C. Camara, A. Carrato, et al.
Randomized study of weekly irinotecan plus high-dose 5-fluorouracil (FUIRI) versus biweekly irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as first-line chemotherapy for patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors Study
Ann. Onc.,
February 1, 2009;
20(2):
251 - 257.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. R. McWhinney, R. M. Goldberg, and H. L. McLeod
Platinum neurotoxicity pharmacogenetics
Mol. Cancer Ther.,
January 1, 2009;
8(1):
10 - 16.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Levi, A. Altinok, J. Clairambault, and A. Goldbeter
Implications of circadian clocks for the rhythmic delivery of cancer therapeutics
Phil Trans R Soc A,
October 13, 2008;
366(1880):
3575 - 3598.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. J. Poston, J. Figueras, F. Giuliante, G. Nuzzo, A. F. Sobrero, J.-F. Gigot, B. Nordlinger, R. Adam, T. Gruenberger, M. A. Choti, et al.
Urgent Need for a New Staging System in Advanced Colorectal Cancer
J. Clin. Oncol.,
October 10, 2008;
26(29):
4828 - 4833.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. R. Alberts and L. D. Wagman
Chemotherapy for Colorectal Cancer Liver Metastases
Oncologist,
October 1, 2008;
13(10):
1063 - 1073.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. H. O'Neil and R. M. Goldberg
Innovations in Chemotherapy for Metastatic Colorectal Cancer: An Update of Recent Clinical Trials
Oncologist,
October 1, 2008;
13(10):
1074 - 1083.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Gruenberger, D. Tamandl, J. Schueller, W. Scheithauer, C. Zielinski, F. Herbst, and T. Gruenberger
Bevacizumab, Capecitabine, and Oxaliplatin As Neoadjuvant Therapy for Patients With Potentially Curable Metastatic Colorectal Cancer
J. Clin. Oncol.,
April 10, 2008;
26(11):
1830 - 1835.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. H. Park, E. Nam, J. Park, E. K. Cho, D. B. Shin, J. H. Lee, W. K. Lee, M. Chung, and S. I. Lee
Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer
Ann. Onc.,
April 1, 2008;
19(4):
729 - 733.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|