High-dose ketoconazole to untreated stage D prostate cancer.

Eleven previously untreated patients with stage D prostate cancer were treated with ketoconazole in a dosage of 400 mg p.o. every 8 h. s-Testosterone was used as a measure of antiandrogen effect. Nine patients had a reduction in s-testosterone to castrate levels (less than 2.9 nmol/l) within 3 days. In the remaining two patients, dose escalation of ketoconazole to 400 mg every 6 h did not lead to sufficient reduction in s-testosterone. Two patients had a complete response and four patients had a partial response of 6/11. Additionally, two patients had bone pain relief without normalization of acid phosphatase. Side-effects and adverse reactions were prominent, causing discontinuation of the treatment in nine patients. It is concluded that high-dose ketoconazole is effective in disseminated prostate cancer, but the high frequency of side-effects makes it less attractive than conventional hormone manipulations like castration or estrogens.