Aminoglutethimide – A New Endocrine Therapy in Breast Cancer

Abstract

Aminoglutethimide is an effective treatment for advanced postmenopausal breast cancer, acting in a novel way. It inhibits peripheral and tumour aromatase, which converts androgens to oestrogens. Marked suppression of oestrone and oestradiol is produced. Aminoglutethimide was used as an inhibitor of adrenal steroid biosynthesis, but the concentrations required to inhibit aromatase in vitro are 10 times lower. This has led to its clinical evaluation in much lower doses. Doses of 125 mg twice daily produce oestrogen suppression equivalent to conventional doses of 1 g daily, and also similar tumour responses. Toxicity is much reduced by the lower dose.

Interactions of aminoglutethimide with analgesics using antinociceptive tests in mice

“…Aminoglutethimide (AG) was initially introduced as an anticonvulsant in 1960 but was withdrawn after it was found to produce adrenal insufficiency. It inhibits an early step in adrenal steroid biosynthesis-the conversion of cholesterol to pregnenolone (Gale 1982;Harris 1985). This inhibition can be overcome by ACTH, so replacement doses of hydrocortisone are also given clinically to block the feedback effect.…”