The treatment of advanced prostate cancer with ketoconazole: safety issues

The definition of hormone refractory prostate cancer is changing. It has become clear that patients with advanced prostate cancer whose disease has progressed following treatment with luteinising hormone releasing hormone agonists and antiandrogens can respond to additional hormonal manoeuvres. Ketoconazole is an imidazole antifungal and the antiandrogen effects of this agent have been known about for over 15 years. Initial concerns about the excessive adverse effects associated with this agent appear to have been overstated. Recent studies have demonstrated that treatment with ketoconazole can produce a significant response in a majority of patients with advanced prostate cancer and that the agent has a reasonable toxicity profile. The most common adverse effect is gastrointestinal intolerance, followed by fatigue, liver function abnormalities and skin changes; the agent is also associated with a variety of rarer adverse effects. The most serious potential adverse effects of the drug can be ameliorated by simple measures.