Novel regimens of capecitabine alone and combined with irinotecan and bevacizumab in colorectal cancer xenografts.

ABSTRACT

BACKGROUND: Xenograft and mathematical models have shown that the antitumor activity of capecitabine can be increased by modifying the schedule from 14 days on, 7 off (14/7) to 7/7. MATERIALS AND METHODS: Capecitabine at two-thirds maximum tolerated dose (MTD) administered using 14/7 (267 mg/kg) and 7/7 (467 mg/kg) schedules, alone and in doublet and triplet combinations with irinotecan (40 mg/kg intraperitoneally) and bevacizumab (5 mg/kg intraperitoneally) were studied in mice bearing HT29 colorectal xenografts. RESULTS: Tumor growth inhibition was >100% in doublet and triplet regimens with capecitabine 7/7 compared with 70% and 98%, respectively, with 14/7. Increase in lifespan was significantly greater with the 7/7 triplet than the corresponding doublet without bevacizumab (288% versus 225%, respectively). CONCLUSION: Addition of bevacizumab to capecitabine and irinotecan significantly improved tumor growth inhibition and lifespan in the HT29 xenograft model. Modifying the capecitabine schedule from 14/7 to 7/7 improved the efficacy of doublet and triplet combinations without toxicity.