Long-term experience with high dose ketoconazole therapy in patients with stage D2 prostatic carcinoma

The antifungal drug ketoconazole has been shown to block testosterone synthesis. High dose ketoconazole therapy was given to 17 patients with previously untreated stage D2 prostatic cancer. Rapid relief of pain occurred in 15 patients with significant pain. Prostatic acid phosphatase levels normalized or decreased in all patients. Bone scan scores were stable or improved. Two patients remain on therapy for more than 30 months. The remainder have ceased treatment owing to subsequent progressive disease (5 patients), side effects (6) or noncompliance. Eleven patients who had relapse after previous endocrine ablative therapy were treated with ketoconazole. Subjective responses were frequent but long-term objective responses were rare. There was a high incidence of side effects, particularly nausea. Ketoconazole may have limited usefulness as initial therapy in patients with endocrine responsive advanced prostatic cancer. The drug can be palliative in some patients who have failed previous therapeutic modalities. Analogues of the drug should prove to have better efficacy and fewer side effects.