New aromatase inhibitors for the treatment of advanced breast cancer in postmenopausal women

Inhibition of the enzyme aromatase, the rate limiting step in estrogen prod uction, is an effective endocrine treatment of advanced postmenopausal brea st cancer. Recently, several new aromatase inhibitors have been developed t o improve efficacy and reduce toxicity compared to the prototype aromatase inhibitor aminoglutethimide. Aromatase inhibitors can be divided into two t ypes. The first are thr non-steroidal inhibitors that have a mechanism of a ction similar to aminoglutethimide. The second are the steroidal inhibitors that function as a false substrate for aromatase. Of the non-steroidal aromatase inhibitors. two drugs, anastrozole and letro zole, have recently been registered for the second line endocrine treatment of advanced postmenopausal breast cancer after failure on tamoxifen. The p hase In studies of these drugs indicate at least equal efficacy compared to current second line treatment with aminoglutethimide or megestrol acetate. Their toxicity profile, however, is much more favourable. This makes them the drugs of choice for the second line endocrine treatment of advanced bre ast cancer in postmenopausal patients, who failed during adjuvant or first line treatment with tamoxifen. Of the steroidal aromatase inhibitors, the orally active drug exemestane is still in phase III clinical study; the registration is expected in 1999. ( C) 1999 Elsevier Science B.V. All rights reserved.