Pivotal trials of letrozole: a new aromatase inhibitor

Oncology (Williston Park). 1998 Mar;12(3 Suppl 5):41-4.


Letrozole (Femara) is a nonsteroidal aromatase inhibitor that is approximately 10,000 times as potent as aminoglutethimide in vivo. Two pivotal multinational phase III trials have compared letrozole (0.5 and 2.5 mg/d) against megestrol acetate and aminoglutethimide, respectively, in patients with locally advanced or metastatic breast cancer. The letrozole vs megestrol acetate trial showed the superiority of letrozole (2.5 mg/d) over megestrol acetate with respect to response rate, response duration, duration of overall clinical benefit (complete response plus partial response plus stable disease > or = 6 months), time to progression, and time to treatment failure. The letrozole-treated patients also showed a nonsignificant trend toward better survival. In the letrozole vs aminoglutethimide trial, letrozole (2.5 mg/d) was significantly superior in terms of duration of overall clinical benefit and survival. There were also strong trends favoring letrozole with regard to objective response rate and duration of response. Unexpectedly, both trials demonstrated a dose-response effect for 2.5 mg of letrozole over 0.5 mg in terms of response and overall survival. This finding raises the possibility that intratumoral aromatase suppression may be more relevant in breast cancer therapy than are plasma estrogen levels.

Publication types

  • Review

MeSH terms

  • Aminoglutethimide / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Aromatase Inhibitors*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Letrozole
  • Megestrol Acetate / therapeutic use
  • Nitriles / therapeutic use*
  • Treatment Outcome
  • Triazoles / therapeutic use*


  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Nitriles
  • Triazoles
  • Aminoglutethimide
  • Letrozole
  • Megestrol Acetate