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.