Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: Results of two randomized double blind controlled multiinstitutional trials

BACKGROUND. Breast cancer patients with prior response to endocrine therapy achieve subsequent benefit from additional endocrine therapies. The efficacy and safely of an aromatase inhibitor, fadrozole HCL, were compared with megestrol acetate in postmenopausal patients who had disease progression after receiving antiestrogen therapy for metastatic disease or as adjuvant therapy. METHODS. In 2 multiinstutional prospective trials, 683 postmenopausal patients were randomized to receive either fadrozole HCL, 1 mg twice daily, or megestrol acetate, 40 mg 4 times daily, in a double blind fashion after progression on first-line hormonal therapy. Objective response rates, time to progression, survival, and safety of the two regimens were compared. RESULTS. Results of intent-to-treat analyses are presented in this study. No significant differences were detected between the two treatment groups in time to progression, objective response rates, duration of response, and survival in either trial. There were no clinically meaningful differences between the treatment groups in the incidence and severity of adverse experiences, except that weight gain, fluid retention, and dyspnea were observed in more patients in the megestrol acetate group compared with those receiving fadrozole HCL, whereas nausea and vomiting were 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 metastatic breast carcinoma after one hormonal therapy. Adverse experiences were mild with both therapies, but megestrol acetate was associated with a higher frequency of weight gain, fluid retention, and dyspnea, whereas fadrozole HCL was associated with a higher frequency of nausea and vomiting.