CYCLOPHOSPHAMIDE AND FLUOROURACIL COMBINED WITH MITOXANTRONE VERSUS DOXORUBICIN FOR BREAST-CANCER - SUPERIORITY OF DOXORUBICIN

Patients and Methods: We conducted ct randomized, multicenter study of intravenous cyclophosphamide 500 mg/m(2) plus fluorouracil 500 mg/m(2 ) combined with either mitoxantrone (Novantrone, Lederle Cyanamid Cana da Ltd, Willowdale, Ontario) 10 mg/m(2) (CNF) or doxorubicin (Adriamyc in, Adria Laboratories of Canada Ltd, Mississauga, Ontario) 50 mg/m(2) (CAF) every 3 weeks in advanced breast cancer. Results: The response rate in 249 randomized patients was 36% with CNF (44 of 121) and 48% w ith CAF (62 of 128) (P=.054), with complete remissions in 10 patients (8.3%) on CNF and in 13 (10.2%) on CAF. If only fully assessable patie nts are considered, the response rate was 48% (44 of 91) with CNF and 60% (62 of 103) with CAF (P=.098). At time of analysis, all except 10 patients (one CNF and nine CAF) had died. The median survival time wit h CAF was longer than with CNF (15.2 v 10.9 months; P=.003), and time to progression was also longer with CAF (5.3 v 3.2 months; P <.03). Su rvival differences remained significant (P=.006) if patients who faile d to meet all eligibility criteria were excluded. bi Favorable prognos tic factors for survival in a Cox regression model included good perfo rmance status (P <.0001); less than two organ systems involved by tumo r (P <.0001); no involvement of lung, liver, or brain (P <.003); invol vement of bone or bone marrow (P <.009), prior surgery for breast canc er (P <.006); being premenopausal (P <.03); greater than or equal to 3 years from diagnosis until randomization on this study (P <.03); and treatment with CAF (P <.03), Alopecia greater than or equal to grade 3 was reported in 55% of patients with CAF and 12% of patients with CNF (P <.001), while other greater than or equal to grade 3 toxicities di d not differ significantly, Priestman-Baum quality-of-life assessment was comparable on the two study arms. Conclusion: In patients with adv anced breast cancer, CAF was associated with longer survival than was CNF, with an increase in alopecia, but not in other toxicities. (C) 19 97 by American Society of Clinical Oncology.