Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer.

BACKGROUND Bevacizumab (Avastin) significantly improves overall survival (OS) and progression-free survival (PFS) when combined with first-line irinotecan (IFL) plus bolus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer (CRC). This open-label, phase IV trial evaluated the efficacy and safety of first-line bevacizumab in combination with IFL and infusional 5-FU/LV (FOLFIRI). METHODS Two-hundred and nine treatment-naïve metastatic CRC patients were enrolled and received bevacizumab and FOLFIRI every 2 weeks. Treatment was continued until disease progression. The primary objective was PFS, with additional determinations of OS, response and toxicity. RESULTS Median PFS was 11.1 months and is comparable to that observed in published phase III and community-based trials using first-line bevacizumab plus FOLFIRI, and to phase III trials using bevacizumab in combination with bolus 5-FU/LV plus IFL. Median OS was 22.2 months. Overall response rate was 53.1% and the disease control rate 85.6%. Most adverse events were grade 1/2 and were manageable. The most common grade 3/4 adverse events (> or =10%) were neutropenia, venous thromboembolic events, diarrhea, and fatigue. CONCLUSION Bevacizumab combined with first-line FOLFIRI is an effective and well-tolerated therapy option for patients with metastatic CRC.