Capecitabine/Cyclophosphamide/Methotrexate for patients with metastatic breast cancer: a dose-finding, feasibility, and efficacy study.

BACKGROUND: Capecitabine is a fluoropyrimidine carbamate that acts as a prodrug, mimics continuous infusion of 5-fluorouracil (5-FU), and has encouraging antitumor activity in women with metastatic breast cancer. We performed a feasibility study in which the 5-FU of the cyclophosphamide/methotrexate/5-FU regimen was substituted with capecitabine in a novel regimen applicable to women with breast cancer. Three doses of capecitabine were explored (1650 mg/m2, 1850 mg/m2, and 2000 mg/m2 per day from day 1 to day 14) in combination with intravenous bolus cyclophosphamide (600 mg/m2) and methotrexate (40 mg/m2), given on day 1 and day 8 every 4 weeks. PATIENTS AND METHODS: From June 2002 to August 2004, 39 women with metastatic breast cancer were enrolled and were evaluable for toxicity and response. RESULTS: Hematologic toxicity was mild for the majority of patients: grade 4 neutropenia and anemia and grade 3 thrombocytopenia occurred in 1 patient. Nonhematologic toxicity of grade > or = 3 occurred only at the highest dose level. Overall response rate was 44% (complete response rate, 13%; partial response rate, 31%). Clinical benefit including long-lasting (> or = 6 months) stable disease overall accounted for 82%. Responses were observed at each dose level. The median duration of response was 14 months (95% confidence interval, 10-28 months). At a median observation of 24 months (range, 8-36 months), time to progression was 13 months (95% confidence interval, 9-24 months). CONCLUSION: The data of our study show that cyclophosphamide/methotrexate/capecitabine is feasible and active. The capecitabine dose of 1850 mg/m(2) orally on days 1-14 every 28 days was selected as the recommended dose in view of the higher likelihood of "on time" chronic therapy compared with the 2000-mg/m(2) dose.