LETROZOLE (CGS-20267), A NEW ORAL AROMATASE INHIBITOR FOR THE TREATMENT OF ADVANCED BREAST-CANCER IN POSTMENOPAUSAL PATIENTS

Letrozole is a new orally, active, potent, and highly specific non-ste roidal aromatase inhibitor. Letrozole is about 200 and 10 000 times as potent as aminaglutethimide (AG) in vitro and in vivo, respectively. Letrozole was tested in healthy men and postmenopausal women and in po stmenopausal patients with advanced breast cancer (ABC). Levels of cir culating estrogens decreased by more than 75 to 95% from pre-treatment levels have been observed in patients treated with daily doses of 0.1 to 5 mg letrozole. No clinically relevant changes in other hormones o f the endocrine system were found. In four phase Ib/IIa trials, letroz ole has shown anti-tumor activity in postmenopausal patients with ABC previously treated with hormonotherapy and/or chemotherapy. Letrozole was well tolerated. Phase IIb/III studies are on going to compare two doses of letrozole with meoestrol acetate or AG in order to confirm th e anti-tumor efficacy of letrozole in the treatment of ABC in postmeno pausal patients who progressed/relapsed following treatment with anti- estrogens.