Phase III trial of cyclophosphamide, epirubicin, fluorouracil (CEF) versus cyclophosphamide, mitoxantrone, fluorouracil (CNF) in women with metastatic breast cancer

Background: The mitoxantrone combination CNF and the epirubicin combination CEF have shown similar activity and less toxicity than the standard CAF combination in metastatic breast cancer (MBC). A prospective randomised study was started to compare safety and activity between CEF and CNF administered using a classical chemotherapeutic schedule in MBC. Patients and methods: From December 1987 to June 1993, 151 patients were randomised to receive cyclophosphamide (C) 100 mg m(-2) p.o. days 1-14, fluorouracil (F) 500 mg m(-2) i.v. days 1 and 8, and epirubicin (E) 30 mg m(-2) i.v. days 1 and 8, or mitoxantrone (N) 6 mg m(-2) i.v. days 1 and 8, every 4 weeks. Seventy-three patients were eligible for CEF and 72 for CNF. Results: Objective responses were observed in 61.6 of the CEF group and 44.4 in CNF group (p=0.004). The median duration of response was 64 weeks in CEF and 50 weeks in CNF group (p=0.02) and median time to progression was 51 and 33 weeks, respectively (p=0.0004). At the time of analysis, all except six patients (one in CNF and five in CEF) had died and the median survival time in the CEF group was longer than in CNF (74.4 weeks vs 51.4 weeks; log-rank chi(2) test p=0.015). CNF produced more hematologic toxicity than CEF (WHO scale; grades 2-4): leucopenia 84% vs 68% (p=0.03) and trombocytopenia 17% vs 4.5% (p=0.01); CEF caused more grade 2 and 3 alopecia: 93% vs 70% (p=0.00 1). Conclusion: The combination CEF using this schedule and dosage in metastatic breast cancer is more effective with less toxicity than CNF, except for alopecia, and was associated with longer survival.