aminoglutethimide + formestane

Aminoglutethimide + formestane is a combination of two steroidogenesis inhibitors used primarily in the treatment of advanced, hormone-sensitive breast cancer in postmenopausal women. Aminoglutethimide is a nonsteroidal aromatase inhibitor and adrenocortical steroid synthesis inhibitor that blocks the conversion of cholesterol to pregnenolone and inhibits several steps in steroid biosynthesis, including aromatization required for estrogen production[2][4]. Formestane (4-hydroxyandrostenedione) is a steroidal aromatase inhibitor that irreversibly binds to and inactivates the aromatase enzyme, leading to significant suppression of plasma estrogen levels[6][8]. The combination has been studied as a means to further reduce circulating estrogens after progression on monotherapy with either agent. While adding aminoglutethimide to formestane can cause an additional drop in plasma estrogens—especially oestrone sulphate—the improvement over single-agent therapy appears marginal and may be due more to enhanced metabolism than increased aromatase inhibition[1][5]. This regimen has been explored mainly as second- or third-line endocrine therapy for heavily pretreated postmenopausal breast cancer patients.