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Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer

Open access
Loupakis, Fotios, Cremolini, Chiara, Masi, Gianluca, Lonardi, Sara, Zagonel, Vittorina, Salvatore, Lisa, Cortesi, Enrico, Tomasello, Gianluca, Ronzoni, Monica, Spadi, Rosella, Zaniboni, Alberto, Tonini, Giuseppe, Buonadonna, Angela, Amoroso, Domenico, Chiara, Silvana, Carlomagno, Chiara, Boni, Corrado, Allegrini, Giacomo, Boni, Luca, Falcone, Alfredo·2014·New England Journal of Medicine

Abstract

BACKGROUND: A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects. METHODS: We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62 to 0.90; P=0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P=0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P=0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group. CONCLUSIONS: FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; ClinicalTrials.gov number, NCT00719797.).

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Metadata

Authors
Loupakis, F., Cremolini, C., Masi, G., Lonardi, S., Zagonel, V., Salvatore, L., Cortesi, E., Tomasello, G., Ronzoni, M., Spadi, R., Zaniboni, A., Tonini, G., Buonadonna, A., Amoroso, D., Chiara, S., Carlomagno, C., Boni, C., Allegrini, G., Boni, L., & Falcone, A.
Venue
New England Journal of Medicine
Published
2014-10-23
Volume
371
Issue
17
Pages
1609-1618
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W1993780950
Cited by
1,062
References
6
FWCI
39.35
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer. https://app.cochat.ai/papers/10.1056/nejmoa1403108
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Loupakis, F., Cremolini, C., Masi, G., Lonardi, S., Zagonel, V., Salvatore, L., Cortesi, E., Tomasello, G., Ronzoni, M., Spadi, R., Zaniboni, A., Tonini, G., Buonadonna, A., Amoroso, D., Chiara, S., Carlomagno, C., Boni, C., Allegrini, G., Boni, L., & Falcone, A. (2014). Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1403108

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.