Additive effects of aminoglutethimide, testololactone, and 4-hydroxyandrostenedione as inhibitors of aromatase.

In vitro p450 spectral data suggested that combinations of aromatase inhibitors might produce enhanced biologic effects. If correct, two clinically available aromatase inhibitors, aminoglutethimide (AG) and testololactone (TL) could potentially be given together at lower than usual dosage with reduction of patient side effects and preservation of aromatase inhibition. Using a [3H]water aromatase assay and a placental microsomal system, AG and TL were tested individually and in combination over their respective dose response ranges. Additive effects of these two compounds were observed. Another inhibitor, 4-hydroxyandrostenedione, given with AG produced similar additive inhibition. These data provide a basis for a future trial of AG and TL in combination in patients with breast carcinoma.