963 Exemestane in postmenopausal patients with advanced breast cancer: A dose-finding study

Exemestane (6-methylenandrosta-1.4-diene-3.17-dione) is a new type I aromarase inhibitor, which is active by the oral route. In a previous experience, we documented the drug's effectiveness in reducing serum oestrogen levels at daily doses ranging from 25 to 2.5 mg and, for this reason, we initiated this further study to determine the minimum effective dose. Exemestane was orally administered to 20 postmenopausal patients with metastatic breast cancer, at daily doses of 5, 2.5, 1 or 0.5 mg. The doses were randomly given under double-blind conditions (5 pts for each dose), and the changes in E 1 , E 2 , E 1 S, LH, FSH, SHGB and DHEAS serum levels were evaluated on days 0, 7, 14, 28 and 56. The pts were considered evaluable providing they had received at least two months of therapy. The hormone analysis is still ongoing, but here we report the data concerning clinical efficacy and tolerability. All of the pts had received previous hormonal therapy for metastatic disease (9 pts > 1 treatment) and 18 had also received chemotherapy (7 as adjuvant treatment and 11 for metastatic disease). The other characteristics of the pts were: median age 56 yrs (range 47–82); ER+/PgR+: 14 pts; DFI ≥ 2 yrs: 15 pts. Soft tissue involvement was documented in 7 pts, bone in 12 and viscera in 14. Irrespective of the dose, 2 PR were obtained on soft tissue and liver; SD with a median duration of 6 months (range 3–14) was observed in 14 pts. Exemestane was very well tolerated, with nausea and asthenia (grade 1 WHO) being reported in 3 and 2 pts respectively. The hormonal data will be provided at the Congress. Data management by I.T.M.O. (Italian Trials in Medical Oncology) Scientific Service .