ENDOCRINOLOGIC AND CLINICAL-EVALUATION OF EXEMESTANE, A NEW STEROIDALAROMATASE INHIBITOR

The androstenedione derivative, exemestane (FCE 24304), is a new orall y active irreversible aromatase inhibitor. Fifty-six post-menopausal a dvanced breast cancer patients entered this study to evaluate the acti vity of four low exemestane doses in reducing oestrogen levels. The dr ug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate level s were evaluated. Drug selectivity was studied by measuring 17-hydroxy corticosteroid urinary levels. After 7 days of treatment, mean oestron e and oestradiol levels had decreased by respectively 64% and 65% (a d ecrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were sign ificantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment t olerability was satisfactory: nausea and dyspepsia were reported in 16 % of patients. The overall objective response rate was 18%. In conclus ion, exemestane is effective in reducing oestrogen levels at all of th e tested doses and shows interesting clinical activity.