Aromatase inhibitors and inactivators are playing an increasing greater role in
breast cancer treatment.
Exemestane, a highly specific, steroidal
aromatase inactivator, is the newest agent in this class. The
drug is highly specific, 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
breast cancer who have failed one or more previous hormonal
therapies.
Exemestane 25 mg/day slows
disease progression and reduces tumour-related signs and symptoms and the
drug exhibits a partial lack of cross-resistance with the non-steroidal
aromatase inhibitors. Response rates to
exemestane of 14% to 29% were observed including patients with visceral
metastases, who have historically proven difficult to treat. In a large phase III trial,
exemestane was found to be superior to
megestrol acetate with respect to time to progression and overall survival. In addition,
exemestane is currently under investigation as first-line
therapy in metastatic disease and in sequence with
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 represents a novel and interesting
drug for the treatment of advanced
breast cancer, with exciting prospects for use in adjuvant
therapy and, potentially,
breast cancer prevention.