Testosterone (androgen)-depleting therapies are usually the first line of defense for men with newly-diagnosed or recurrent prostate cancer. But resistance to these therapies develop over time which leaves the patient and physicians with a number of choices as to the next sequence of therapies to be administered. Recently, guidelines, issued jointly by the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) in Canada, highlight recent advances in treating this more advanced form of prostate cancer. Six new treatments have been approved in the last two years for the treatment of prostate cancer and its symptoms. However, opinions differ as to the sequence of using these therapies and their cost, their relationships to a man’s quality of life, the disease stage of the cancer, and prior therapies received by the patient. Combination studies are certainly needed and underway. The new guidelines for hormone therapy – resistant tumors that have metastasized are based on a review of 56 randomized clinical trials published since 1979 and include the following recommendations.
a) Continue hormone-deprivation therapy indefinitely. b) In addition to hormone deprivation, offer patients one of three treatment options including Zytiga® (abiraterone acetate and prednisone), Xtandi® (enzalutamide), or alpha-radin (radium-223 chloride if the cancer has spread to the bones). All three treatments are associated with improved survival, quality of life and a favorable balance of benefit and harms. c) When considering chemotherapy, taxotere (docetaxel®) with prednisone should be an option but side effects must be discussed. See also the September 20th, 2014 blog. d) Offer cabazitaxel to men whose disease worsens even if taxotere has been tried, but again discuss the side effects. e) Offer Provenge® (sipuleucel-T) to men with no or minimal cancer symptoms. Some physicians maintain that it can be most effective to initially stimulate the immune system with agents like Provenge® before other agents are utilized. f) Offer mitoxantrone but include a discussion of the drug’s limited clinical benefit and side effect risk. Mitoxantrone is also used to treat leukemias and multiple sclerosis. g) Offer ketoconazole or the anti-androgen therapies bicalutamide, flutamide or nilutamide but discuss the limited clinical benefits of these three medications. h) Do not offer other anti-cancer drugs such as bevacizumab (Avastin®), estramustine or sunitinib. i) Begin discussions of palliative care early on while discussing treatment options.
The experts on the panel formulating these guidelines said the optimum sequence in which various treatments should be given remains unclear, but “ongoing clinical trials are exploring this question, as well as potential benefits of combining various treatments.”