Randomized, open-label, phase II trial of oral capecitabine (Xeloda®) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer

Background: Oral capecitabine was evaluated in terms of overall response rate, safety, and tolerability as first-line therapy in women aged greater than or equal to 55 years with advanced/metastatic breast cancer. Patients and methods: Ninety-five patients were randomized (2 : 1) to either intermittent oral capecitabine 1255 mg/m(2) twice daily (two weeks' treatment followed by a one-week rest period) or intravenous CMF (cyclophosphamide, methotrexate, 5-fluorouracil [5-FU]) administered every three weeks. Results: The overall response rate in the capecitabine group was 30% (95% confidence interval (95% CI): 19%-43%), including three complete responses (5%). The response rate observed in the CMF group was 16% (95% CI: 5%-33%), with no complete responses. Median time to disease progression was 4.1 months with capecitabine and 3.0 months with CMF. Survival was similar in the two treatment groups (median 19.6 months with capecitabine, 17.2 months with CMF). The safety profiles were different for capecitabine and CMF. However, both regimens were generally well tolerated and treatment interruption and/or dose modification was effective in managing toxicities associated with capecitabine. Alopecia and myelosuppression were rare in patients receiving capecitabine while diarrhea and hand-foot syndrome were more common. Treatment interruption and/or individual dose adjustment of capecitabine was required in 34% of patients and was generally effective in managing adverse events. Treatment was stopped owing to toxicity in 16% of patients in the capecitabine arm. The incidence of deaths during or within 28 days of stopping study treatment was 8% and 6% in the capecitabine and CMF arms, respectively. Conclusions: An oral, twice-daily regimen of capecitabine is effective and well tolerated when used as first-line chemotherapy in older patients (greater than or equal to 55 years) with advanced/metastatic breast cancer, and is suitable for outpatient therapy.