Mineralocorticoid insufficiency due to suramin therapy

Ken Kobayashi, Roy E Weiss, Nicholas J. Vogelzang, Everett E. Vokes, Linda Janisch, Mark J. Ratain

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 of treatment or immediately after discontinuation of treatment. RESULTS. Two of 9 patients (22%) treated at relatively low dose levels (≤ 1200 mg/m2 on Day 1) demonstrated adrenal cortical insufficiency, as compared with 9 of 11 patients (82%) 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.

Original languageEnglish (US)
Pages (from-to)2411-2420
Number of pages10
JournalCancer
Volume78
Issue number11
DOIs
StatePublished - Dec 1 1996
Externally publishedYes

Fingerprint

Suramin
Mineralocorticoids
Glucocorticoids
Therapeutics
Hydrocortisone
Carcinoma
Adrenal Insufficiency
Aldosterone
Antineoplastic Agents
Prostate
Hormones

Keywords

  • adrenal cortical insufficiency
  • dose response
  • dose toxicity
  • fludrocortisone
  • glucocorticoid
  • hydrocortisone
  • mineralocorticoid
  • suramin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kobayashi, K., Weiss, R. E., Vogelzang, N. J., Vokes, E. E., Janisch, L., & Ratain, M. J. (1996). Mineralocorticoid insufficiency due to suramin therapy. Cancer, 78(11), 2411-2420. https://doi.org/10.1002/(SICI)1097-0142(19961201)78:11<2411::AID-CNCR20>3.0.CO;2-2

Mineralocorticoid insufficiency due to suramin therapy. / Kobayashi, Ken; Weiss, Roy E; Vogelzang, Nicholas J.; Vokes, Everett E.; Janisch, Linda; Ratain, Mark J.

In: Cancer, Vol. 78, No. 11, 01.12.1996, p. 2411-2420.

Research output: Contribution to journalArticle

Kobayashi, K, Weiss, RE, Vogelzang, NJ, Vokes, EE, Janisch, L & Ratain, MJ 1996, 'Mineralocorticoid insufficiency due to suramin therapy', Cancer, vol. 78, no. 11, pp. 2411-2420. https://doi.org/10.1002/(SICI)1097-0142(19961201)78:11<2411::AID-CNCR20>3.0.CO;2-2
Kobayashi, Ken ; Weiss, Roy E ; Vogelzang, Nicholas J. ; Vokes, Everett E. ; Janisch, Linda ; Ratain, Mark J. / Mineralocorticoid insufficiency due to suramin therapy. In: Cancer. 1996 ; Vol. 78, No. 11. pp. 2411-2420.
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abstract = "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 of treatment or immediately after discontinuation of treatment. RESULTS. Two of 9 patients (22{\%}) treated at relatively low dose levels (≤ 1200 mg/m2 on Day 1) demonstrated adrenal cortical insufficiency, as compared with 9 of 11 patients (82{\%}) 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.",
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AU - Weiss, Roy E

AU - Vogelzang, Nicholas J.

AU - Vokes, Everett E.

AU - Janisch, Linda

AU - Ratain, Mark J.

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N2 - 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 of treatment or immediately after discontinuation of treatment. RESULTS. Two of 9 patients (22%) treated at relatively low dose levels (≤ 1200 mg/m2 on Day 1) demonstrated adrenal cortical insufficiency, as compared with 9 of 11 patients (82%) 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.

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KW - hydrocortisone

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