PIVOTAL TRIALS OF LETROZOLE - A NEW AROMATASE INHIBITOR

Letrozole (Femara) is a nonsteroidal, aromatase inhibitor that is appr oximately 10,000 times as potent as aminoglutethimide in vivo., Two pi votal multinational phase III trials have compared letrozole (0.5 and 2.5 mg/d) against megestrol acetate and aminoglutethimide, respectivel y, iii patients with locally advanced or metastatic breast cancer The letrozole vs megestrol acetate trial showed the superiority of letrozo le (2.5 mg/d) over megestrol acetate with respect to response Fate, re sponse duration, duration of overall clinical benefit (complete respon se plus partial response plus stable disease greater than or equal to 6 months), time to progression, and time to treatment failure. The let rozole-treated patients also showed a nonsignificant trend toward bett er survival. In the letrozole vs aminoglutethimide trial, letrozole (2 .5 mg/d) was significantly superior in terms of duration of overall cl inical benefit and survival. There were also strong trends favoring le trozole with regard to objective response rate and duration of respons e. Unexpectedly, both trials demonstrated a dose-response effect for 2 .5 mg of letrozole over 0.5 mg in terms of response and overall surviv al, This finding raises the possibility that intratumoral aromatase su ppression may be more relevant in breast cancer therapy than are plasm a estrogen levels.