Aromatase inhibitors: clinical pharmacology and therapeutic implications in breast cancer.

Aminoglutethimide was the first aromatase inhibitor to be used in breast cancer therapy but, since it interacts with the synthetic glucocorticoids, hydrocortisone must also be given as a replacement. The most important side-effects of aminoglutethimide are at the level of the central nervous system. Other aromatase inhibitors with greater potency and selectivity are being developed. Pyridoglutethimide, a compound resulting from modifications to the structure of aminoglutethimide, seems to be devoid of sedative properties according to preliminary tests on the central nervous system. 4-Hydroxyandrostenedione is significantly more potent and better tolerated than aminoglutethimide. Fadrozole (CGS 16,949 A) is 200-400 times more potent than aminoglutethimide and is now in phase II of its clinical development. CGS 20,267 has no effect on adrenal steroidogenesis and is currently in phase I of its clinical development. Availability of newer aromatase inhibitors could make a worthwhile contribution to endocrine therapy in breast cancer.