OBJECTIVE: The present study aimed to identify the recommended dose (RD) of capecitabine, epirubicin and cyclophosphamide (CEX) combination treatment for inoperable or metastatic breast cancer and to assess response rate, tolerability and pharmacokinetics in Japanese patients. METHODS: Patients received 3-week cycles of fixed-dose intravenous cyclophosphamide (600 mg/m(2), day 1), intravenous epirubicin (75-100 mg/m(2), day 1) and oral capecitabine (628-900 mg/m(2) twice daily, days 1-14). Dose escalation/deescalation decisions for consecutive cohorts were made using the continual reassessment method (CRM). RD was defined as dose level closest to that causing dose-limiting toxicity (DLT) in 33% of patients. RESULTS: Among the 17 patients enrolled, 3 experienced DLT (hand-foot syndrome, anorexia, mucositis; all grade 3) and 3 (18%) febrile neutropenia. Based on CRM calculation, mean DLT occurrence probabilities (90% confidence intervals in parentheses) for levels 2, 3 and 4 were 21% (8-42%), 35% (17-56%) and 56% (38-71%), respectively. Level 3 was thus chosen as the RD. Combination treatment did not affect pharmacokinetic parameters of capecitabine, epirubicin or their metabolites. Objective responses were achieved by 7 patients (41%), including partial responses in 4 of 6 patients (67%) receiving the RD. CONCLUSION: CEX represents a well-tolerated regimen, and RD for Japanese patients was determined to be capecitabine 900 mg/m(2) twice daily in combination with epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) using the CRM. (c) 2008 S. Karger AG, Basel