Selective aromatase inhibition for patients with androgen-independent prostate carcinoma: A phase II study of letrozole

BACKGROUND. First and second-generation aromatase inhibitors have shown activity in patients with androgen-independent prostate carcinoma. These early-generation aromatase inhibitors are nonselective, however, and inhibition of other steroidogenic enzymes may contribute to their reported clinical activity. The authors conducted a Phase II clinical study of letrozole to determine the safety and efficacy of a potent and selective third- generation aromatase inhibitor in men with androgen-independent prostate carcinoma. METHODS. Forty-three men with androgen-independent prostate carcinoma were treated with oral letrozole (2.5 mg daily). Treatment was continued until progressive disease or Grade 3 toxicity developed. Response and progressive disease were defined according to recommendations of the Prostate Specific Antigen Working Group. RESULTS. In total, 380 weeks of treatment were administered to the 43 study patients. The median duration of treatment was 8 weeks. Forty men discontinued treatment due to progressive disease. Only one patient responded to treatment with a sustained decrease > 50% in serum prostate specific antigen (PSA) levels. Three other patients experienced transient minor decreases (< 50%) in serum PSA levels. There were no serious treatment-related adverse events. CONCLUSIONS. Selective aromatase inhibition with letrozole is not active in men with androgen-independent prostate carcinoma.