Mitoxantrone, cyclophosphamide, and fluorouracil in metastatic breast cancer unresponsive to hormonal therapy.

Fifty-two patients with hormonally unresponsive or estrogen receptor negative metastatic breast cancer who had not received prior chemotherapy received mitoxantrone 10 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 1000 mg/m2 (MCF) by short intravenous infusion every 21 days. Disease that was resistant or stable to this regimen was treated with doxorubicin 25 mg/m2/day for two days and vinblastine 1.4 mg/m2/day for four days (DV). Both drugs were given by continuous infusion. Thirty-one partial remissions and four complete remissions occurred after treatment with MCF. Only thirty-four evaluable patients crossed to the DV phase with partial remission (11 patients), stable (five patients), or resistant (18 patients) disease. Eleven patients' responses were upgraded. The median overall time to progression (TTP), defined as the sum of the TTP on MCF and TTP on DV, was 12 months. The median survival of all patients was 19 months. Granulocytopenia was the dose limiting toxicity for MCF, but cumulative thrombocytopenia was noted. Nausea and vomiting occurred in most patients but was mild. Severe alopecia occurred in half the patients. One patient developed congestive heart failure after receiving a cumulative dose of 206 mg/m2 of mitoxantrone. The incidence of infectious complications was 35% on each regimen; 50% of these were mild. MCF is an effective combination that was well tolerated. Objective responses, durations of response, and survival were similar, but not superior, to standard doxorubicin-based combinations. Toxicity was somewhat less.