A phase II study of oxaliplatin, capecitabine and bevacizumab in the treatment of metastatic colorectal cancer

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3556 Background: Bevacizumab (BV), a monoclonal antibody directed against vascular endothelial growth factor, provides a survival advantage when added to first line therapy for metastatic colorectal cancer. The FOLFOX regimen is superior to bolus IFL, but requires the inconvenience of an ambulatory infusion pump. We aimed to investigate the combination of capecitabine, oxaliplatin and bevacizumab (XeloxA) as a more convenient and active regimen. Methods: Patients with untreated metastatic colorectal cancer received oxaliplatin 85 mg/m 2 day 1, capecitabine 1000 mg/m 2/bid days 1–5 and 8–12, and BV 10 mg/kg day 1. Cycles were repeated every 2 weeks. The starting dose of capecitabine was changed to 850 mg/m 2/bid due to toxicity in the first 27 patients. Patient data were analyzed under an intention to treat method.. Results: Thirty patients received therapy: 16 men, 14 women, median age 55.5 (range 24–76). Diarrhea was prominent occurring at any grade in 22/30 (73%) patients, although only 9/30 (30%) had grade 3 diarrhea and no patient experienced grade 4 diarrhea. Of the three patients started at the 850 mg/m2/bid dose of capecitabine, none have experienced > grade 1 diarrhea. Hand-foot syndrome (HFS) was seen in most patients; 6/30 (20%) with grade 1, 12/30 (40%) with grade 2 and 1/30 (3%) with grade 3 HFS. Other toxicities were minimal including grade 3 neutropenia (7%), grade 3 nausea and vomiting (7%), and grade 3 peripheral neuropathy (10%). Twenty patients (66%) required at least one dose reduction of capecitabine, and 12/30 (40%) required 2 or more dose reductions during treatment, typically for diarrhea and/or HFS. There were sixteen partial responses and one complete response (RR=57%; 95% CI: 37% -75%). Eleven (37%) patients had stable disease. Median time to progression was 11.9 months (95% CI: 9.8 to ∞). Conclusions: Preliminary evidence suggests that the XeloxA regimen is highly active. The reported median time to progression is among the highest yet obtained in the first line treatment of metastatic colorectal cancer. The initial capecitabine dosing schedule was decreased due to toxicity, and thus far appears to be better tolerated. Enrollment will continue to a planned accrual of 50 patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Roche Genentech