The influence of CGS 16949A on peripheral aromatisation in breast cancer patients.

The influence of a new aromatase inhibitor, CGS 16949A on peripheral aromatisation of androstenedione into oestrone was investigated in postmenopausal women with breast cancer. A mixture of 3H androstenedione and 14C oestrone was injected, and all urine was collected for the following 96 h. The isotope ratio was determined in the urinary oestrogen metabolites after isolation by HPLC. Eight patients were investigated before and during treatment with CGS 16949A. At a dose of 1 mg b.d. (eight patients) CGS 16949A inhibited aromatisation by a mean value of 82.4% (range 71.3 to 93.7%). When the drug dose was escalated to 2 mg b.d. (three patients) aromatisation was inhibited by a mean of 92.6% (range 90.6 to 95.8%), these results suggest that CGS 16949A at a dose of 1 mg b.d. causes submaximal aromatase inhibition in many patients, while a dose of 2 mg b.d. seems to result in greater than 90% aromatase inhibition. These data are consistent with previous observations that the higher dose is more effective in suppression of plasma oestradiol levels.