BACKGROUND Fadrozole hydrochloride (CGS-16949A) belongs to the class of aromatase inhibitors that lowers circulating estrogen levels by inhibiting the conversion of androgens to estrogens, thereby causing tumor regression in patients with breast carcinoma. METHODS This was a prospective, randomized, Phase II study of fadrozole hydrochloride in postmenopausal patients with metastatic breast carcinoma. The three treatment groups received, respectively, fadrozole hydrochloride 0.6 mg three times daily, 1 mg twice daily, and 2 mg twice daily orally. RESULTS Fifty-six patients were entered on protocol and 54 were eligible (2 patients were perimenopausal). Eight patients had received no prior therapy, 15 patients had received prior hormonal therapy, 5 patients had received prior chemotherapy, and 28 patients had received both. After 12 weeks of treatment, 2 complete and 3 partial responses were observed. Forty patients continued treatment beyond 12 weeks, and 3 additional responses were achieved. Thus, 8 of 56 patients responded (14% overall response rate). Responses did not appear to be dose-related. The median duration of response was 36 months (range, 8-45 months). Subjective toxicity was mild to moderate and appeared more frequent on the 2 mg twice daily dosing schedule. No objective toxicity in laboratory parameters was observed. No patient had severe or life-threatening toxicity. Fadrozole hydrochloride plasma concentrations (obtained every 2 weeks for 12 weeks) appeared to be dose-dependent and noncumulative. CONCLUSIONS This study confirms modest activity of fadrozole hydrochloride in a heterogeneous group of patients with breast carcinoma treated at three different dose levels.