FADROZOLE HCL (CGS-16949A) VERSUS MEGESTROL-ACETATE TREATMENT OF POSTMENOPAUSAL PATIENTS WITH METASTATIC BREAST-CARCINOMA - RESULTS OF 2 RANDOMIZED DOUBLE-BLIND CONTROLLED MULTIINSTITUTIONAL TRIALS

BACKGROUND. Breast cancer patients with prior response to endocrine th erapy achieve subsequent benefit from additional endocrine therapies. The efficacy and safety of an aromatase inhibitor, fadrozole HCL, were compared with megestrol acetate in postmenopausal patients who had di sease progression after receiving antiestrogen therapy either for meta static disease or as adjuvant therapy. METHODS. In 2 multiinstitutiona l prospective trials, 683 postmenopausal patients were randomized to r eceive either fadrozole HCL, 1 mg twice daily, or megestrol acetate, 4 0 mg 4 times daily, in a double blind fashion after progression on fir st-line hormonal therapy. Objective response rates, time ro progressio n, survival, and safety of the two regimens were compared. RESULTS. Re sults of intent-to-treat analyses are presented in this study. No sign ificant differences were detected between the two treatment groups in time to progression, objective response rates, duration of response, a nd survival in either trial. There were no clinically meaningful diffe rences between the treatment groups in the incidence and severity of a dverse experiences, except that weight gain, fluid retention, and dysp nea were observed in more patients in the megestrol acetate group comp ared with those receiving fadrozole HCL, whereas nausea and vomiting w ere observed in more patients in the fadrozole HCL group compared with those receiving megestrol acetate. CONCLUSIONS. Fadrozole HCL was as efficacious as megestrol acetate in postmenopausal patients with metas tatic breast carcinoma after one hormonal therapy. Adverse experiences were mild with both therapies, but megestrol acetate was associated w ith a higher frequency of weight gain, fluid retention, and dyspnea, w hereas fadrozole HCL was associated with a higher frequency of nausea and vomiting. (C) 1996 American Cancer Society.