Pharmacology and clinical experience with exemestane

Since the introduction of the first generation aromatase inhibitor, aminoglutethimide, for breast cancer treatment 30 years ago, we now have at hand novel, potent and well-tolerated steroidal and non-steroidal compounds, allowing near complete inhibition of oestrogen synthesis. The third-generation aromatase inhibitor, or more accurately termed inactivator, exemestane, is a potent suppressor of oestrogen synthesis and is shown to be an effective antitumour agent in postmenopausal breast cancer patients. Exemestane has been shown to be effective in patients failing multiple endocrine regimens. A large randomised study has revealed that exemestane improves time-to-disease progression as well as overall survival compared with megestrol acetate as second-line therapy in patients failing tamoxifen. In current studies, exemestane is compared with tamoxifen as first-line therapy for metastatic disease. Sequential therapy with tamoxifen followed by exemestane is also being compared with tamoxifen monotherapy in the adjuvant setting. In addition, the drug may have potential for breast cancer prevention.