IN-VIVO INHIBITION OF AROMATIZATION BY EXEMESTANE, A NOVEL IRREVERSIBLE AROMATASE INHIBITOR, IN POSTMENOPAUSAL BREAST-CANCER PATIENTS

The effect of exemestane (6-methylenandrosta-1,4-diene-3,17-dione) 25 mg p.o. once daily on in vivo aromatization was studied in 10 postmeno pausal women with advanced breast cancer. Aromatization was determined before treatment and after 6-8 weeks on therapy by administering a bo lus injection of [H-3]androstenedione (500 mu Ci) and [C-14]estrone (5 mu Ci) followed by measurement of the isotope ratio of urinary estrog ens after high-performance liquid chromatography purification. In addi tion, plasma endogenous estrogens mere measured with highly sensitive radioimmunoassays after separation with high-performance liquid chroma tography. Treatment with exemestane suppressed whole body aromatizatio n from a mean pretreatment value of 2.059% to 0.042% (mean suppression of 97.9%). Plasma levels of estrone, estradiol, and estrone sulfate w ere found to be suppressed by 94.5%, 92.2%, and 93.2%, respectively. T his is the first study revealing near total aromatase inhibition in vi vo with the use of a steroidal aromatase inhibitor. The observation th at exemestane is a highly potent aromatase inhibitor, together with th e fact that the drug is administered p.o. and causes limited side effe cts, suggests that exemestane is a promising new drug for the treatmen t of hormone sensitive breast cancer.