Advanced prostate cancer will progress and most of us will face a time when Androgen Deprivation Therapy (ADT) stops working. Most men on ADT take a LHRH agonist, which turns off the production of testosterone (i.e. Lupron) along with a non-steroidal anti-androgen (i.e. Casodex) that prevents the small amount of testosterone that continues to be produced from entering into the prostate cancer cell.
When ADT fails, the next step is to discontinue the use of the anti-androgen. At the cellular level, for a not yet understood reason, the anti-androgen modifies its functioning and instead of blocking the testosterone, it begins to fuel the growth of the cancer itself. Stopping the anti-androgen deprives the cancer of this new fuel source, often resulting in the quieting of the cancer growth and the lowering of the PSA.
It is inevitable that even after the stopping of the anti-androgen the cancer will again begin to progress. Doctors may then choose to prescribe a different anti-androgen, Nilandron (nilutamide). Nilandron uses different pathways than Casodex, so it sometimes can be successfully used as a replacement for Casodex. Along with the continued use of the LHRH agonist and a 5AR inhibitor that some doctors also prescribe, Nilandron can be effective in controlling the cancer and PSA. However, Nilandron does not work for all men, but for some it will work for several months or even years.
In the cases when Nilandron does not work or when it too fails, another alternative treatment to consider is either low dose or high dose ketoconazole (LDK or HDK). A corticosteroid is usually administered along with the LDK or HDK. Ketoconazole (which is actually an anti-fungal medication) assists the LHRH agonist in stopping the testicular production of testosterone as well as a “turning off” the adrenal gland, which is responsible for the production of androgen precursors. Just like chemotherapy, LDK and HDK can be toxic so very careful and have your liver functions monitored.
Once these therapies have become ineffective, taxane chemotherapy still is available to extend your life. Taxane therapy, like all the other therapies discussed can have significant side effects and can be toxic. Careful monitoring while on any of these therapies is vital.
The goal of all these therapies is to extend your life long enough to allow you to take advantage of new therapies as they become available. Unfortunately, there are no therapies on the horizon that hold the promise of a cure for prostate cancer. The name of the game when fighting advanced prostate cancer is life extension.
Joel T Nowak MA, MSW