High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects

High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty pat...

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Bibliographic Details
Published in:Journal of clinical oncology Vol. 7; no. 8; p. 1093
Main Authors: Trump, D L, Havlin, K H, Messing, E M, Cummings, K B, Lange, P H, Jordan, V C
Format: Journal Article
Language:English
Published: United States 01-08-1989
Subjects:
Acid Phosphatase - blood
Aged
Aged, 80 and over
Androstenedione - blood
Antigens, Neoplasm - analysis
Biomarkers, Tumor - analysis
Diethylstilbestrol - therapeutic use
Drug Evaluation
Humans
Hydrocortisone - therapeutic use
Ketoconazole - administration & dosage
Ketoconazole - therapeutic use
Male
Middle Aged
Orchiectomy
Pituitary Hormone-Releasing Hormones - therapeutic use
Prostate - analysis
Prostate-Specific Antigen
Prostatic Neoplasms - drug therapy
Testicular Hormones - antagonists & inhibitors
Testosterone - blood
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Summary:High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.
ISSN:0732-183X
DOI:10.1200/jco.1989.7.8.1093