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Prostate cancer is the most common nonskin cancer in American men, and androgen-deprivation therapy is the cornerstone of treatment for advanced prostate cancer. Unfortunately, the median duration of response to initial androgen deprivation is limited to 18-24 months. After failing primary therapy, many individuals respond to multiple secondary hormonal interventions, such as ketoconazole. A potent adrenolytic agent, ketoconazole is associated with potential hepatotoxicity, adrenal insufficiency, and drug and food interactions. Nurses can greatly impact the course of treatment for patients by being aware of the rationale for the use of secondary hormones, ketoconazole as a hormonal intervention, potential drug interactions, side effects, and management of toxicities.