ABSTRACT
Adrenalectomy had been effective in the management of breast cancer, but many patients were poor operative risks. A medical ablation of adrenal function would have wider application. Aminogluthimide 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 1.0-2.5 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. Tumour growth ceased for 4 and 7 months in two patients. Suppression of urinary 17-ketosteroids and 17-hydroxycorticosteroids was only transient in 8 patients, presumably because of compensatory increase in ACTH secretion. Oestrogen secretion rates were similarly affected. The patient with a 9-month remission on 2.5 g daily demonstrated permanent hypoadrenocorticism. Dose-related CNS toxicity ranging from drowsiness to semicoma predominated, but relative hypoadrenocorticism may have contributed. The authors suggested that anticancer action may result from a peripheral effect of the drug or from suppression of an unidentified steroid. Concurrent pharmacological doses of glucocorticoids may reduce toxicity and inhibit compensatory ACTH secretion.
