Suramin, a
drug known to have
antiparasitic effects, has been previously shown to have adrenocorticolytic activity in primates. We now confirm preferential accumulation of this compound in the normal adrenal gland, evaluate its in vitro effect against two human
adrenocortical carcinoma cell lines (SW-13 and NCI-H295), and report the clinical activity of
suramin in 17 patients with metastatic
adrenocortical carcinoma. Inhibition of colony formation occurred in both adrenal cell lines in vitro at concentrations that are clinically achievable in humans. In addition,
suramin concentrations as low as 100 micrograms/mL were able to inhibit
glucocorticoid,
mineralocorticoid, and
androgen production by the NCI-H295 cell line. Of 16 patients with
adrenocortical carcinoma now evaluable for
tumor response, 2 achieved a partial response, 2 had a minor response, and 5 remained with stable disease for periods ranging from 3-10 months; the remainder progressed. One of 7 patients with excessive
steroid hormone production achieved a partial normalization of her
steroid levels for the duration of
suramin therapy in the setting of radiographic disease stabilization. An additional patient treated off-study for lack of radiographically measurable disease, achieved complete normalization of plasma
aldosterone levels. We conclude that
suramin preferentially accumulates in adrenal cells, induces cytotoxicity and significant down-regulation of
steroid hormone production in vitro, and has some therapeutic efficacy as a single agent in patients with metastatic
adrenocortical carcinoma.