New aromatase inhibitors

Tamoxifen still is the mainstay of endocrine therapy in women with advanced breast cancer. Response rates in hormone receptor-positive patients are re ported in about 50%. Second-line therapy so far consisted of high-dosed pro gestins such as megestrolacetate or of the first-generation aromatase inhib itor aminoglutethimide. Though the objective remission rates still are abou t 25-30%, these drugs have a considerable side effect potential. The first selective aromatase inhibitor introduced was the steroid aromatase inhibito r 4-hydroxyandrostenedione (4-OHA). Due to a high first-pass effect. 4-OHA has to be applicated parenterally. The higher selectivity leads to a better tolerability. In a next step, highly selective, orally applicable aromatas e inhibitors were developed. These third-generation aromatase inhibitors su ch as letrozole, anastrozole or vorozole combine high remission rates and l ow side effect potential with the possibility of oral daily application. In phase II and III studies these new aromatase inhibitors could show their s uperiority over progestins. Letrozole and vorozole even achieved higher rem ission rates than aminoglutethimide. Therefore the third-generation aromata se inhibitors should be used in the second-line therapy of advanced breast cancer after failure of tamoxifen. Trials are in progress to test the use o f the new aromatase inhibitors in the adjuvant or first-line therapy.