Ketoconazole (kee-ta-KOE-na-zol), generic name for Nizoral, is an oral drug approved by the FDA for the use to treat fungal infections. However, it has been shown that higher doses of ketoconazole (800-1200mg/day vs 200-400mg/day) also block the production of both free and bound testosterone. Since high-dose Ketoconazole (HDK) has testosterone lowering effects, operating both on the testicular and the adrenal production of androgens, it can be used as an unapproved androgen deprivation therapy (ADT) for the treatment of advanced recurrent prostate cancer.

Normally, HDK is used after the traditional (LHRH agonists – Lupron & Zoladex) ADT methods have stopped working. Thus, HDK is often referred to as a secondary hormone manipulation has it can have a positive effect the prostate cancer growth even after the LHRH drugs have failed. The physical mechanisms in the body used by HDK are different then those used by the LHRH drugs and are often able to lower the PSA, even after the prostate cancer is referred to as being hormone refractory.

There is also additional evidence that HDK has a direct cytotoxic (creating cell death) effect on some lines of prostate cancer cells. Hydrocortisone (HC) is added to the ketoconazole (HDK) in order to replace the natural cortisol production that is inhibited by the HDK.

Scholz and Strum have shown that the positive effects of HDK can be prolonged if the baseline PSA is lower then 10.0 prior to commencing the use of the HKD. In addition, men with prostate cancer commonly report pain reduction from bone metastasis when they take HDK.

There are many common side effects from HDK. They include complaints of weakness, gastrointestinal problems (including nausea and vomiting), liver toxicity, adrenal suppression, edema, anorexia and skin irritation.

Some doctors are hesitant to use HDK because of the potential liver toxicity. A system of careful and regular monitoring of liver enzyme levels must put in place when using HDK to treat prostate cancer patients safely. It is very important that before taking Ketoconazole, tell your doctor if you have liver disease, kidney disease, a heart rhythm disorder or decreased stomach acid (achlorhydria).

David Emerson, who has taken ketoconazole, has very kindly written about his personal experience using it. David did have a positive effect from the drug; sadly, it no longer is working for him. David has just started taking chemotherapy with Taxotere.

David has very kindly written about his experience with HDK for this blog. Tomorrow, I will post his inside experience. Remember, each man’s prostate cancer is different and each man experiences both good and bad effects from treatments will differ.

Joel T Nowak MA, MSW