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

Abstract

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.