Selective aromatase inhibition for patients with androgen‐independent prostate carcinoma

• Published in: Cancer 2002-11, Vol.95 (9), p.1864-1868
• Main Authors: Smith, Matthew R., Kaufman, Donald, George, Daniel, Oh, William K., Kazanis, Maryanne, Manola, Judith, Kantoff, Philip W.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Androgens; androgen‐independent; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; aromatase; Aromatase Inhibitors; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Estradiol - blood; Humans; letrozole; Male; Middle Aged; Neoplasms, Hormone-Dependent - drug therapy; Nitriles - adverse effects; Nitriles - therapeutic use; prostatatic neoplasms; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Sex Hormone-Binding Globulin - analysis; Testosterone - blood; Triazoles - adverse effects; Triazoles - therapeutic use
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.10844

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. Cancer 2002;95:1864–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10844 Treatment with letrozole, a potent and selective third‐generation aromatase inhibitor, was inactive in men with androgen‐independent prostate carcinoma. These results suggest that the reported activity of nonselective first and second‐generation aromatase inhibitors results from inhibition of other steroidogenic enzymes.