LETROZOLE (CGS-20267) - A PHASE-I STUDY OF A NEW POTENT ORAL AROMATASE INHIBITOR OF BREAST-CANCER

Background. Letrozole (CGS 20267), a triazole derivative, is a new, on ce-daily, oral nonsteroidal inhibitor of aromatase activity. Methods. In this Phase I trial, 23 heavily pretreated postmenopausal patients w ith metastatic breast cancer received letrozole at doses ranging from 0.1 to 5.0 mg once daily. Results. No hematologic, biochemical, or sig nificant clinical toxicity was encountered. Serial steroid measurement s were determined in 19 of these patients. Letrozole at all doses test ed 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 c ompromise glucocorticoid or mineralocorticoid production or thyroid fu nction. Of the 21 evaluable patients, there were 2 with partial respon ses and 7 with stable disease. Conclusions. Letrozole is a well tolera ted, potent, and specific inhibitor of estrogen biosynthesis in postme nopausal patients with metastatic breast cancer.