A Phase II Study of the Global Dose and Schedule of Capecitabine in Japanese Patients with Metastatic Colorectal Cancer

Abstract

Background: Although the standard 3-week capecitabine regimen (1250 mg/m² twice daily for 2 weeks followed by a 1-week rest) has shown superior activity and improved safety over bolus 5-fluorouracil/leucovorin in two large randomized phase III trials in Europe and in the United States, only a 4-week regimen of capecitabine (828 mg/m² twice daily for 3 weeks) has been studied in Japan. Therefore, we performed a phase II study to investigate the 3-week regimen of capecitabine in Japanese patients with metastatic colorectal cancer (MCRC). Methods: Previously untreated patients with MCRC received oral capecitabine 1250 mg/m² twice daily for 2 weeks. Treatment was repeated every 3 weeks. Blood and urine samples were collected for pharmacokinetic analysis. Results: Sixty patients were enrolled. The overall response rate was 35% [95% confidence interval (CI), 23–48%], and 52% of patients had stable disease. The median time to progression was 5.5 months (95% CI, 4.2–6.7 months). The median overall survival was 20.2 months (95% CI, 16.6–27.8 months). The most frequently occurring adverse drug reaction was hand-foot syndrome (all-grade 73%; grade 3 13%). Diarrhea, anorexia, nausea and stomatitis were each seen in 37% of patients. The pharmacokinetic profiles of capecitabine and its metabolites were similar to those reported in Caucasian patients. Conclusions: The 3-week regimen of capecitabine was effective and well tolerated in Japanese patients with MCRC as well, and could be used as the basic regimen for future combination therapies.