A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.

Abstract

PURPOSE The study investigated the therapeutic effects of fadrozole (CGS 16949A), a new aromatase inhibitor, in women who had received prior treatment for metastatic breast cancer. MATERIALS AND METHODS Eighty postmenopausal women who had received prior treatment for metastatic breast cancer were randomized to receive fadrozole 1 mg/d or 4 mg/d per day orally. Seventy-eight patients were assessable for toxicity and response. RESULTS Toxicity was limited to mild (grade 1) to moderate (grade 2) hot flashes in 28%, nausea and vomiting in 13%, fatigue in 8%, and mild loss of appetite in 5% of patients. No electrolyte or unanticipated hormonal changes occurred. The overall response was 23% (complete response, 10%; partial response, 13%). In addition, 45% of the patients had a no change status. There was no difference in response rate between the patients randomized to the two different doses of fadrozole. Only dominant site of metastases significantly affected response. The median time to treatment failure (TTF) was 4.4 months (4.7 months on 1 mg/d and 3.7 months on 4 mg/d). The median survival was 22.6 months (17.5 months on 1 mg/d; median survival has not been reached in patients on 4 mg/d). The response and survival in patients with estrogen receptor (ER)-positive and ER-unknown disease were not significantly different. CONCLUSIONS Fadrozole has good therapeutic effect as a second-line treatment in postmenopausal women with metastatic breast cancer. In this study there was no significant difference in toxicity or response between 1 mg/d and 4 mg/d. Further trials comparing fadrozole to other hormone treatment are indicated.