Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer

Richard J. Santen, Eugeniusz Samojlik, Allan Lipton, Harold Harvey, Edward B. Ruby, Samuel A. Wells, John Kendall

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Abstract

Approximately one‐third of patients with metastatic breast carcinoma respond to surgical ablative therapy but the morbidity associated with these procedures has limited their use to highly selected patients. Consequently, a chemical method of adrenal suppression was developed using a potent inhibitor of adrenal steroid synthesis, aminoglutethimide, in combination with a synthetic glucocorticoid, dexamethasone. While this regimen effectively blocked adrenal function, it was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism and reduced the bioavailability of dexamethasone. To overcome this problem, a new regime using aminoglutethimide and hydro‐cortisone, a glucocorticoid less susceptible to altered metabolism, was developed. Kinetic studies confirmed that aminoglutethimide does not interact with hydrocortisone to alter its rate of metabolism. Hormone measurements established that 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily suppressed DHA‐sulfate, androstenedione, estrone, estradiol and aldosterone to a greater extent than the prior protocol using aminoglutethimide and 2–3 mg of dexamethasone. Patients experienced objective tumor regression with equal frequency while receiving the aminoglutethimide‐hydrocortisone regimen or aminoglutethimide and dexamethasone and the overall rate of response in 50 evaluable patients was 38%. Side effects occurred frequently in the first few weeks of treatment but disappeared nearly uniformly thereafter. The present aminoglutethimide‐hydrocortisone regimen is simple, non‐toxic, effective in inhibiting estradiol synthesis and capable of inducing tumor regression as frequently as previously reported with adrenalectomy.

Original languageEnglish (US)
Pages (from-to)2948-2958
Number of pages11
JournalCancer
Volume39
Issue number6
DOIs
StatePublished - Jun 1977

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Santen, R. J., Samojlik, E., Lipton, A., Harvey, H., Ruby, E. B., Wells, S. A., & Kendall, J. (1977). Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer. Cancer, 39(6), 2948-2958. https://doi.org/10.1002/1097-0142(197706)39:6<2948::AID-CNCR2820390681>3.0.CO;2-9