THE MINIMAL EFFECTIVE EXEMESTANE DOSE FOR ENDOCRINE ACTIVITY IN ADVANCED BREAST-CANCER

Phase I studies have demonstrated that exemestane, an irreversible ora l aromatase inhibitor, is able to suppress circulating oestrogen level s. In our previous experience, doses ranging from 2.5 to 25 mg induced a similar suppression of oestrogens. The aim of this study was to ide ntify the minimum effective exemestane dose on the basis of endocrine activity. 20 evaluable postmenopausal advanced breast cancer patients were randomly given exemestane 0.5, 1, 2.5 or 5 mg, in double-blind co nditions. Oestrone (E1), oestradiol (E2), oestrone sulphate (E1S), gon adotrophins, sex-hormone binding globulin and dehydroepiandrosterone s ulphate serum levels were evaluated from the first day of treatment to the 7th, 14th, 28th and 56th day. Serum E1, E2 and E1S levels were su ppressed by all doses starting from day 7; the degree of inhibition ve rsus baseline was 25 up to 72% for E1, 30 up to 62% for E2 and 16 up t o 52% for E1S, with higher doses achieving greater suppression; these changes were maintained over time. A significant increase in FSH and L H levels was observed for all doses. Treatment tolerability was satisf actory. The endocrine effects of exemestane appear to be dose related and 0.5 and 1 mg are ineffective for adequately suppressing circulatin g oestrogens. (C) 1997 Elsevier Science Ltd.