A PHASE-III RANDOMIZED TRIAL OC CYCLOPHOSPHAMIDE, MITOXANTRONE, AND 5-FLUOROURACIL (CNF) VERSUS CYCLOPHOSPHAMIDE, ADRIAMYCIN, AND 5-FLUOROURACIL (CAF) IN PATIENTS WITH METASTATIC BREAST-CANCER

One hundred patients with metastatic breast cancer were randomly selec ted to receive combined chemotherapy treatment with adriamycin (50 mg/ m(2)) or mitoxantrone (12 mg/m(2)) associated with 5-fluorouracil (600 mg/m(2)) and cyclophosphamide (600 mg/m(2)) administered intravenousl y every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherap y for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statis tically significant differences in pretreatment characteristics or met astatic disease location between the two groups. Ninety-four patients were assessable for response, No differences were observed in response rate or in survival between the groups. The response rate (complete r esponse (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients we re assessable for toxicity. There were no differences in gastrointesti nal and cardiac toxicity. More grade I-II hematologic toxicity episode s (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were o bserved with the CNF group, and more grade III alopecia (p < 0.001) wa s observed with the CAF group, Patients received further therapeutic m anoeuvres after finishing the study with a sequential treatment consis ting of hormonal therapy and chemotherapy with mitomycin (M) -vinblast ine (Vbl) (M 10 mg/m(2) day 1, Vbl 5 mg/m(2) days 1, 15 and 29; maximu m 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34 % and grade III-IV hematologic toxicity of 37 %. Treatment with CNF can be considered a good alternative to CAF f or first-line treatment of metastatic breast cancer. M-Vbl treatment i s useful as second-line treatment in patients with prior adriamycin ex posure.