MINERALOCORTICOID INSUFFICIENCY DUE TO SURAMIN THERAPY

BACKGROUND. During a Phase I trial of suramin, a novel antineoplastic agent with activity against hormone-refractory prostate carcinoma, the authors observed two patients with clinical mineralocorticoid insuffi ciency in spite of hydrocortisone replacement therapy. METHODS. The au thors retrospectively assessed adrenal cortical function in 20 such pa tients via adrenocorticotropic stimulation resting, measuring both cor tisol and aldosterone responses, either at the time of treatment or im mediately after discontinuation of treatment. RESULTS. Two of 9 patien ts (22%) treated at relatively low dose levels (less than or equal to 1200 mg/ m(2) on Day 1) demonstrated adrenal cortical insufficiency, a s compared with 9 of 11 patients (82%) treated with relatively high do ses (>1200 mg/m(2) on Day I) (P = 0.03 by 1-tailed Fisher's exact test ). There appeared to be a cumulative dose-response relationship to the development of glucocorticoid insufficiency, with no instances being observed at doses < 4.8 g/m(2) and uniform toxicity occurring at doses > 7.6 g/m(2). Long term glucocorticoid insufficiency was present in 1 of 5 patients (20%) tested at an interval of >90 days after discontin uation of suramin treatment. All instances of glucocorticoid insuffici ency were associated with mineralocorticoid insufficiency. Suramin did not affect the absorption or excretion of exogenously administered gl ucocorticoid in one patient. CONCLUSIONS. Suramin causes both primary mineralcorticoid and primary glucocorticoid insufficiency. This may oc cur in a dose-dependent manner. Long term glucocorticoid insufficiency appears to occur in a minority of patients treated with low doses of suramin. Patients receiving high doses of suramin for treatment of adv anced carcinoma should receive at least physiologic replacement doses of both mineralocorticoid and glucocorticoid. Higher doses of glucocor ticoid may be required in selected patients. (C) 1996 American Cancer Society.