Phase I/II study of bi-weekly XELIRI plus bevacizumab treatment in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy.

PURPOSE: We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy.

METHODS: Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm(2) and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2-8. Each 2-week treatment cycle was defined as a single course of treatment. During Phase I, we determined the recommended dose for capecitabine. In Phase II trials, efficacy and treatment safety was verified (UMIN000003934).

RESULTS: The recommended dose of capecitabine was determined to be 2000 mg/m(2). Median progression-free survival was 7.8 months [95% confidence interval (CI) 6.1-10.9 months], and median overall survival was 18.9 months (95% CI 11.6-28.4 months). Response rate was 17.4% (95% CI 6.4-28.3%). The most common Grade ≥3 hematotoxic adverse events were anemia (10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of Grade ≥3 non-hematotoxic adverse events was relatively low (<10%).

CONCLUSION: Bi-weekly XELIRI plus bevacizumab was found to be a safe and effective second-line treatment in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy.