A phase II study of capecitabine, irinotecan, and bevacizumab in patients with previously untreated metastatic colorectal cancer.

BACKGROUND: Previous phase III studies raised concern about the safety of the combination of capecitabine and irinotecan in patients with metastatic colorectal cancer (mCRC). We conducted a single arm phase II study to evaluate the safety and efficacy of bevacizumab in combination with dose-reduced capecitabine and irinotecan in patients with previously untreated mCRC.

PATIENTS AND METHODS: Patients with previously untreated mCRC were eligible. Capecitabine was given at 1,000 mg/m2 orally twice daily for 14 days and dose was reduced to 750 mg/m2 for patients over 65. Irinotecan was given at 200 mg/m2 and bevacizumab was given at 7.5 mg/kg intravenously on day 1. The treatment cycle was repeated every 21 days. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival, response rate, and toxicity.

RESULTS: Fifty patients were enrolled, the median age was 58, and 54% were ECOG 0. The most common grade 3/4 adverse events included hand-foot syndrome (14%), neutropenia (12%), and diarrhea (10%). Response rate was 51% and disease control rate (response and stable disease) was 98%. Median PFS was 11.5 months (95% CI: 9.2-13.7), and 6 month PFS was 90% (95% CI: 77-98%).

CONCLUSION: With modest dose reductions, the combination of capecitabine, irinotecan, and bevacizumab was well tolerated and resulted in favorable outcomes for patients with previously untreated mCRC.