At some point in the progression of advanced prostate cancer the usual initial standard of care, hormone therapy (ADT2 or ADT3), will fail to control the progression of the cancer. Commonly, when ADT does fail we will experience an increase in our PSA scores and often see signs of disease progression on imaging tests. For many men this signifies a new stage of their disease.
The first thing we need to do is verify that the ADT has actually failed. If you have not been actively monitoring your testosterone levels (which you should be doing) you need to get your testosterone level checked, this can be done with a simple blood test. If your testosterone level is above 20 ng/dl then you have not reached or have not maintained the castrate level required to enjoy the benefits of the therapy. If your level is higher you should point this out to your doctor and discuss what changes maybe need to push your testosterone level below 20 ng/dl.
If your level is below 20 ng/dl and you have an increasing PSA level or have demonstrated disease progression as evidenced by scans you have become castrate resistant. Now the question becomes what next?
Doctors who don’t treat many men with prostate cancer will often recommend that they move on to chemotherapy using taxotere. However, there are a number of alternative treatments available that can still control the disease. These are referred to as 2nd line hormone therapy manipulations. Not all of these treatments will work for all men, but you can try them and see if you do get any benefit.
Ketoconazole (Keto) suppresses the adrenal gland’s production of androgens, including testosterone as well as directly killing prostate cancer cells. Keto should be the first 2nd line hormone therapy you try.
Dr. Eric Small, in a clinical trial, showed that Keto works in 50% of men who are castrate resistant. Usual dosing of Keto is 400 mg every eight hours on an empty stomach; however this dosage can cause significant nausea, vomiting, fatigue and possible liver damage. Dr. Small has also had success reducing the dose to only 200 mg every eight hours with a reduction of the side effects. At this lower dosage the Keto still demonstrated efficacy. Keto has a very short half-life it needs to be taken religiously every eight hours around the clock.
Most experienced physicians also give hydrocortisone along with the Keto to combat the adrenal insufficiency which often develops. The usual dosage of the hydrocortisone is 20 mg. with breakfast and then 10mg or 20mg with dinner.
Keto is absorbed in the stomach, best under acidic conditions. It is highly recommended that the drug be taken with an acidic beverage like Coke, Pepsi or fruit juice (never with grapefruit juice which blocks CYP3A4, a required liver protein). So not to block its absorption, keto should be taken at least 30 to 60 minutes before or two hours after food intake.
Drs. Schultz & Strum have shown that ketoconazole therapy can be effective for a significantly longer time period if it is started while the base PSA is under 10.
Keto also blocks the CYP3A4 protein, thus taking Keto will hamper your ability to use many other drugs like antibiotics or statins. All of your doctors need to know you are taking Keto so they can review your medications and make any necessary adjustments to your regimes.
(FYI- Keto is not FDA approved for use as a second line hormone therapy drug for prostate cancer.)
The next post about 2nd line hormone manipulations will be about using estrogens to control the cancer.
Joel T Nowak, M.A., M.S.W.