Cetuximab plus FOLFIRINOX (ERBIRINOX) as first-line treatment for unresectable metastatic colorectal cancer: a phase II trial

Abstract

Background: Triplet chemotherapy has demonstrated manageable toxicities and a favorable response rate. The addition of cetuximab to chemotherapy can increase treatment efficacy. We evaluated the efficacy and safety of cetuximab plus 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), the ERBIRINOX regimen, as first-line treatment in patients with unresectable metastatic colorectal cancer (mCRC).

Patients and methods: In a phase II study, treatment consisted of weekly cetuximab plus biweekly. Treatment was continued for a maximum of 12 cycles and tumor response was evaluated every four cycles. The primary efficacy criterion was the complete response (CR) rate.

Results: From April 2006 to April 2008, 42 patients were enrolled. The median age was 60 years (range, 32-76 years). The median duration of treatment was 5.2 months (range, 0.7-8.5 months), and a median of nine cycles was given per patient (range, 1-12 cycles). Five patients (11.9%) showed a CR, with a median duration of 23.1 months (95% confidence interval [CI], 10.8-39.7 months). The objective response rate was 80.9% (95% CI, 65.9%-91.4%). The median overall and progression-free survival times were 24.7 months (95% CI, 22.6 months to not reached) and 9.5 months (95% CI, 7.6-10.4 months), respectively. The most frequent grade 3-4 adverse events were diarrhea (52%), neutropenia (38%), and asthenia (32%).

Conclusion: The ERBIRINOX regimen appears to be effective and feasible in first-line treatment of mCRC patients. These promising results led us to initiate a multicenter, randomized, phase II trial ([Research Partnership for Digestive Oncology] PRODIGE 14) in patients with potentially resectable mCRC.

Figure 1.

Trial profile.

Figure 2.

Overall survival and progression-free survival. Shown are Kaplan–Meier curves for overall survival (A) and progression-free survival (B) in the study population. Abbreviation: ERBIRINOX, cetuximab plus 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin.

Figure 3.

Patient response rate according to KRAS status. Thirty-five patients were available for both KRAS status and tumor response evaluation. Red, mutated KRAS; blue, wild-type KRAS.

Figure 4.

Overall survival and progression-free survival according to KRAS status. Shown are Kaplan–Meier curves for overall survival (A) and progression-free survival (B) according to KRAS status. Abbreviation: ERBIRINOX, cetuximab plus 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin.