내분비요법저항성 전립선암에서의 Ketoconazole과 Prednisolone 복합요법의 경험

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 predinisolone 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 200mg ketoconazole orally every 8 hours and 5mg prednisolone orally every 12 hours. Mean follow-up period was 6 months(1-15 months). Results: Overall, of 8 evaluabel 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 Only 1 patient was withdrawn due to possible ketoconazole-related toxicity.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. (Korean J Urol 1998; 39: 1001~5)" Key word : Ketoconazole, Prednisolone, Hormone refractory prostate cancer