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अमूर्त

Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared with Infusional Fluorouracil, Levcovorin, and Irinotecan (FOLFIRI) as First-Line Treatment for Metastatic Colorectal Cancer

Aly M. Azmy, Khalid Elhusseiny Nasr, Nagy Samy Gobran and Mohamed Yassin Mostafa

Rationale: This phase III study was conducted to compare fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first line management of metastatic colorectal carcinoma. Methods: Sixty patients with unresectable metastatic colorectal adenocarcinoma were randomly assigned to FOLFOXIRI (n = 30) or FOLFIRI (n = 30) as first line for metastatic disease. The primary end point was response rate (RR) and secondary end points were progression free survival (PFS), overall survival (OS), post chemotherapy RO surgical resection (complete resection with safety margin), and toxicity. Results: The RR was significantly higher for FOLFOXIRI arm 60% (18/30) compared to FOLFIRI (33%) (p = 0.007). The rate of progression was significantly lower for patients treated with FOLFOXIRI (11% vs. 24%; p = 0.02), 5 patients (16%) underwent radical (RO) surgery of metastases in the FOLFOXIRI arm compared with one patient (3%) in the FOLFIRI arm (p = 0.02). FOLFOXIRI resulted in an increased PFS, with median PFS of 10 month vs. 7.5 months (p = 0.0099) with an HR for progression of 2.58 (95% CI, 1.2 to 5.3). The rate of early progression (patients who progressed within six months from the treatment onset) was significantly lower in the FOLFOXIRI arm (18% vs. 45%; p < 0.0001); OS is significantly longer for FOLFOXIRI (22.6 vs. 16.7 months; p = 0.032) corresponding to an HR for death of 0.70 (95% CI, 0.50 to 0.96). Patients who received FOLFOXIRI were subjected to significantly higher incidence of adverse events; grade 2 to 3 peripheral neurotoxicity (0% vs. 20%; p < 0.001) and grade 3 to 4 neutropenia (26% vs. 53%; p < 0.001). Febrile neutropenia was comparable between the two arms (3% vs. 6%) of patients; p = 2. Conclusion: Compared to FOLFIRI regimen; FOLFOXIRI regimen has significantly higher RR, PFS, OS, and improved chance for resection of metastases, with higher but tolerable toxicity in patients with metastatic colorectal cancer.