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.
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.
Authors: Hua Li; Peng Wang; Quanhong Sun; Wen-Xing Ding; Xiao-Ming Yin; Robert W Sobol; Donna B Stolz; Jian Yu; Lin Zhang Journal: Cancer Res Date: 2011-03-28 Impact factor: 12.701
Authors: L Heijmen; C J A Punt; E G W Ter Voert; L F de Geus-Oei; A Heerschap; J Bussink; C G J Sweep; V Zerbi; W J G Oyen; P N Span; O Boerman; H W M van Laarhoven Journal: Invest New Drugs Date: 2013-01-17 Impact factor: 3.850
Authors: P García-Alfonso; A J Muñoz-Martin; S Alvarez-Suarez; Y Jerez-Gilarranz; M Riesco-Martinez; P Khosravi; M Martin Journal: Br J Cancer Date: 2010-10-26 Impact factor: 7.640