Ketoconazole with Prednisolone for the Treatment of Hormone Refractory Prostate Cancer.
- Author:
Byung Tae LEE
1
;
Chun Il KIM
Author Information
1. Department of Urology, Keimyung University School of Medicine, Taegu, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Ketoconazole;
Prednisolone;
Hormone refractory prostate cancer
- MeSH:
Adrenal Cortex Hormones;
Adrenocorticotropic Hormone;
Androgens;
Cytochrome P-450 Enzyme System;
Edema;
Flutamide;
Follow-Up Studies;
Goserelin;
Humans;
Ketoconazole*;
Nausea;
Prednisolone*;
Prostate*;
Prostatic Neoplasms*;
Prostatic Neoplasms, Castration-Resistant;
Vomiting
- From:Korean Journal of Urology
1998;39(10):1001-1005
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Corticosteroids suppress the pituitary production of adrenocorticotropic hormone resulting in decreased adrenal steroid production, including adrenal androgens. Ketoconazole is an imidazole fungal agent that inhibit both testicular and adrenal androgenesis. Its primary mechanism of action is inhibition of a cytochrome P450 dependent step in the steroid synthesis pathway, although it has also been reported to have a direct cytotoxic effect in vitro. The effect of further adrenal androgen blockade with ketoconazole plus prednisolone was studied in 9 patients with prostatic cancer who previously progressed after standard hormone therapy. MATERIALS AND METHODS: We treated 9 patients who had hormone refractory metastatic prostate cancer(goserelin acetate, 3 cases; combined goserelin acetate and flutamide, 6 cases) with 200 mg ketoconazole orally every 8 hours and 5 mg prednisolone orally every 12 hours. Mean follow-up period was 6 months(1-15 months). Results: Overall, of 8 evaluable patients 3 had greater than a 50% decrease, 2 had stable and 3 had increase in PSA. The median duration of response was 4 months. Pain was improved in 4 patients. Ketoconazole was generally well tolerated. Toxicity was mild. Nausea with vomiting, edema and hepatotoxicity occurred in 6, 4, 1 patients, respectively. Only 1 patient was withdrawn due to possible ketoconazole-related toxicity. CONCLUSIONS: We concluded that ketoconazole with prednisolone may be a useful treatment modality for management of patients with hormone refractory prostatic cancer.
