Preliminary trial of aminoglutethimide in breast cancer

Abstract

Adrenalectomy has been effective in the treatment of metastatic breast cancer, but many patients are poor operative risks. A medical ablation of adrenal function would have wider application. Aminoglutethimide blocks adrenal steroidogenesis high in the biosynthetic pathway. Nine patients with absent ovarian function and enlarging metastases received the drug in daily oral doses of 1.0 to 2.5 g. Corticosteroid replacement consisted of dexamethasone 0.75 mg daily and fludrocortisone acetate 0.1 mg every other day. Regression of osseous disease and disappearance of skin metastases were observed in three patients for 7, 9, and 2 months, respectively. Tumor growth ceased for 4 and 7 months in two patients. Suppression of urinary 17-ketosteroids and 17-hydroxycorticoids was only transient in eight patients, presumably because of compensatory increase in ACTH secretion. Estrogen secretion rates were similarly affected. The patient with a 9-month remission on 2.5 g daily has demonstrated permanent hypoadrenocorticism. Dose-related CNS toxicity, ranging from drowsiness to semi-coma, predominated but relative hypoadrenocorticism may have contributed. Anticancer action may result from a peripheral effect of the drug or from suppression of an unidentified steroid. Concurrent pharmacologic doses of glucocorticoids may reduce toxicity and inhibit compensatory ACTH secretion.