A phase I/II study of capecitabine given on a week on/week off schedule combined with bevacizumab and oxaliplatin for patients with untreated advanced colorectal cancer

Background: A week on/week off capecitabine schedule with oxaliplatin/bevacizumab was evaluated in patients with metastatic colorectal cancer (mCRC). Patients and Methods: Forty patients were required. The projected median progression-free survival (PFS) was 12 months (81% power, 1-sided level 0.1 log-rank test). Capecitabine dose was 2500 mg/m2/day on days 1-7 (n = 11) and was increased to 3000 mg/m²/day (n = 29) in combination with oxaliplatin (85 mg/m²) and bevacizumab (5 mg/kg). Cycles were repeated every 2 weeks. Results: Patient characteristics included Eastern Cooperative Oncology Group (ECOG) performance status 0 (n = 24) or 1 (n = 15); median age of 62 years (range, 38-81 years). Median cycles administered were 7 (range, 1-25), corresponding to 3.5 months' treatment duration. Pertinent grade 3/4 toxicities seen were diarrhea (18%), hand-foot syndrome (10%), and peripheral neuropathy (10%). Bowel perforation in 1 patient (3%) and 1 death due to a cerebral hemorrhage (3%) were noted. Response rate (RR) was 38% (1 complete and 14 partial responses). Median PFS was 8.6 months (95% confidence interval [CI], 4.7-10.2 months). Median overall survival was 17.2 months (95% CI, 10.4-24.2 months). Conclusion: The first US experience of capecitabine to our knowledge (3000 mg/m2 on days 1-7) in combination with oxaliplatin/ bevacizumab in mCRC does not appear to have advantages compared with current standard first-line mCRC treatment regimens.