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 insufficiency in spite of hydrocortisone replacement therapy.


METHODS
The authors retrospectively assessed adrenal cortical function in 20 such patients via adrenocorticotropic stimulation testing, measuring both cortisol and aldosterone responses, either at the time or treatment of immediately after discontinuation of treatment.


RESULTS
Two of 9 patients (22%) treated at relatively low dose levels (< or = 1200 mg/m2 on Day 1) demonstrated adrenal cortical insufficiency, as compared with 9 of 11 patients (32%) treated with relatively high doses (> 1200 mg/m2 on Day 1) (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/m2 and uniform toxicity occurring at doses > 7.6 g/m2. Long term glucocorticoid insufficiency was present in 1 of 5 patients (20%) tested at an interval of > 90 days after discontinuation of suramin treatment. All instances of glucocorticoid insufficiency were associated with mineralocorticoid insufficiency. Suramin did not affect the absorption or excretion of exogenously administered glucocorticoid in one patient.


CONCLUSIONS
Suramin causes both primary mineralocorticoid and primary glucocorticoid insufficiency. This may occur 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 advanced carcinoma should receive at least physiologic replacement doses of both mineralocorticoid and glucocorticoid. Higher doses of glucocorticoid may be required in selected patients.
Kobayashi
K
K
Department of Medicine, University of Chicago Pritzker School of Medicine, Illinois, USA.
Weiss
R E
RE
Vogelzang
N J
NJ
Vokes
E E
EE
Janisch
L
L
Ratain
M J
MJ
D000224:Addison Disease / Q000097:blood / Q000139:chemically induced*; D000303:Adrenal Cortex Diseases / Q000097:blood / Q000139:chemically induced*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003366:Cosyntropin; D004334:Drug Administration Schedule; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy; D012189:Retrospective Studies; D013498:Suramin / Q000009:adverse effects* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003366:Cosyntropin; D000450:Aldosterone; D013498:Suramin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone