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
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Purpose: The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m 2 day 1, oxaliplatin 85 mg/m 2 day 1, leucovorin 200 mg/m 2 day 1, fluorouracil 3,200 mg/m 2 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.
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For patients deemed able to tolerate more aggressive therapy, the inclusion of both irinotecan and oxaliplatin together with 5-FU/LV in FOLFOXFIRI triplet chemotherapy improved ORR, PFS, and median OS relative to doublet therapy.
“For patients deemed able to tolerate more aggressive therapy, the inclusion of both irinotecan and oxaliplatin together with 5-FU/LV in FOLFOXFIRI triplet chemotherapy improved ORR, PFS, and median OS relative to doublet therapy [142].”
From Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment (2024) · cites this paper as [142]
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- Authors
- Falcone, A., Ricci, S., Brunetti, I., Pfanner, E., Allegrini, G., Barbara, C., Crinò, L., Benedetti, G., Evangelista, W., Fanchini, L., Cortesi, E., Picone, V., Vitello, S., Chiara, S., Granetto, C., Porcile, G., Fioretto, L., Orlandini, C., Andreuccetti, M., & Masi, G.
- Affiliations
- Ospedale di Macerata (IT)
- University of Pisa (IT)
- Azienda Ospedaliera di Perugia (IT)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2007-05-01
- Volume
- 25
- Issue
- 13
- Pages
- 1670-1676
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2106845199
- Cited by
- 1,241
- References
- 29
- Citations by year
- 2026: 27 · 2025: 35 · 2024: 48 · 2023: 54 · 2022: 66 · 2021: 67 · 2020: 74 · 2019: 70 · 2018: 64 · 2017: 64 · 2016: 65 · 2015: 68 · 2014: 89 · 2013: 65 · 2012: 87
- FWCI
- 37.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- metastatic colorectal cancer, FOLFOXIRI, FOLFIRI, oxaliplatin, irinotecan, 5-fluorouracil, leucovorin, first-line chemotherapy, response rate, peripheral neurotoxicity, neutropenia, diarrhea, liver metastasis, secondary resection, treatment toxicity
- MeSH terms
- Irinotecan, Oxaliplatin, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Leucovorin, Female, Fluorouracil, Humans, Male, Middle Aged, Neoplasm Metastasis, Organoplatinum Compounds, Quality of Life, Recurrence, Colorectal Neoplasms, Survival Analysis
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