Letrozole (CGS 20267). A phase I study of a new potent oral aromatase inhibitor of breast cancer

Cancer. 1995 Apr 15;75(8):2132-8. doi: 10.1002/1097-0142(19950415)75:8<2132::aid-cncr2820750816>3.0.co;2-u.


Background: Letrozole (CGS 20267), a triazole derivative, is a new, once-daily, oral nonsteroidal inhibitor of aromatase activity.

Methods: In this Phase I trial, 23 heavily pretreated postmenopausal patients with metastatic breast cancer received letrozole at doses ranging from 0.1 to 5.0 mg once daily.

Results: No hematologic, biochemical, or significant clinical toxicity was encountered. Serial steroid measurements were determined in 19 of these patients. Letrozole at all doses tested produced a marked suppression of plasma estrone, estradiol, estrone sulfate, and urine estrone and estradiol. This was observed within 24 hours of the initial dose of letrozole and resulted in a greater than 90% suppression of plasma and urinary estrogen levels within 2 weeks. Letrozole appears to be highly selective in its action and does not compromise glucocorticoid or mineralocorticoid production or thyroid function. Of the 21 evaluable patients, there were 2 with partial responses and 7 with stable disease.

Conclusions: Letrozole is a well tolerated, potent, and specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Aromatase Inhibitors*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Estrogen Antagonists / therapeutic use
  • Female
  • Humans
  • Letrozole
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / enzymology
  • Neoplasms, Hormone-Dependent / metabolism
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Remission Induction
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*


  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Estrogen Antagonists
  • Nitriles
  • Triazoles
  • Letrozole