Exemestane: a review of its clinical efficacy and safety

Aromatase inhibitors and inactivators are playing an increasing greater rol e in breast cancer treatment. Exemestane, a highly specific, steroidal arom atase inactivator, is the newest agent in this class. The drug is highly sp ecific, and inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple clinical trials among patients with metastatic bre ast cancer who have failed one or more previous hormonal therapies. Exemest ane 25 mg/day slows disease progression and reduces tumour-related signs an d symptoms and the drug exhibits a partial lack of cross-resistance with th e non-steroidal aromatase inhibitors. Response rates to exemestane of 14% t o 29% were observed including patients with visceral metastases, who have h istorically proven difficult to treat. In a large phase III trial, exemesta ne was found to be superior to megestrol acetate with respect to time to pr ogression and overall survival. In addition, exemestane is currently under investigation as first-line therapy in metastatic disease and in sequence w ith tamoxifen in the adjuvant setting. Adverse events include low-grade hot flashes, nausea, and fatigue - mostly of mild to moderate intensity - and treatment-related discontinuations are rare. In conclusion, exemestane repr esents a novel and interesting drug for the treatment of advanced breast ca ncer, with exciting prospects for use in adjuvant therapy and, potentially, breast cancer prevention. (C) 2001 Harcourt Publishers Ltd.