Selective aromatase inhibition for patients with androgen-independent prostate carcinoma

Cancer. 2002 Nov 1;95(9):1864-8. doi: 10.1002/cncr.10844.

Abstract

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgens*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • 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*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Sex Hormone-Binding Globulin / analysis
  • Testosterone / blood
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*

Substances

  • Androgens
  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Nitriles
  • Sex Hormone-Binding Globulin
  • Triazoles
  • Testosterone
  • Estradiol
  • Letrozole
  • Prostate-Specific Antigen