Most men with advanced or recurrent prostate cancer respond well to hormone therapy. As described elsewhere, hormone therapy works by depriving prostate cancer of androgens (male hormones), so it is frequently called androgen deprivation therapy (ADT). Unfortunately, though, prostate cancer can eventually begin to grow in spite of being deprived of male hormones. Various terms have been used to define these cancers---the one’s that “relapse” or continue to grow after having been contained by initial hormone therapy. Some of these terms include hormone resistant prostate cancer, castration resistant prostate cancer, and hormone refractory prostate cancer.

The diagnosis of hormone resistant prostate cancer is often a serious development for a man fighting prostate cancer, as it can be accompanied by a fairly grim prognosis. However, treating HRPC is one of the most studied areas in prostate cancer research, so new therapies are becoming available each year, and old ones are being improved and refined.  Some of these treatments are outlined below, but first, here are some important things to consider if you have been told that you have hormone resistant prostate cancer.

• Consider adding to your medical team. You want the best and most up-to-date medical advice possible, so it may be beneficial for you to seek out specialists or physicians doing research in this field. Also, it might be practical for you to broaden the base of your local medical team, especially if you and your current physicians anticipate changes in your health or to your treatment regime.
• Consider joining a “Warriors” group. Many PCCN support groups have subgroups of men who are fighting hormone refractory prostate cancer. These subgroups are traditionally called “Warriors”---e.g.,  the PCCN Calgary Warriors or the PCCN Ottawa Warriors.  These “Warriors” groups can provide access to first-hand knowledge and experience in the management of advanced prostate cancer, as well as information about new developments in treatment and about upcoming clinical trials in the area.
• Learn as much as you can, and be proactive about your health and treatment. You will be told that, at this stage, your cancer cannot be cured, which is discouraging. But there are treatments that will prolong your life and preserve its quality. And new research into HRPC may help you continue your fight against prostate cancer well into the future. You can also review your diet and the supplements and vitamins you are taking, get your exercise, get enough sleep, protect your immune system, and take other measures to keep your fighting spirit and body in good shape. Your determination to remain as healthy as you can and to work with your medical team to keep cancer at bay will only help.

Treatments
There are three main categories of system-wide treatment for hormone refractory prostate cancer: secondary hormone therapy, chemotherapy, and immunotherapy. Additionally, there are complementary treatments that help manage pain or metastases to the bone, and there are new and experimental treatments.

Secondary Hormone Therapy
Oddly enough, when initial hormone therapy doesn’t work any longer, a standard treatment is secondary hormone therapy.  Sometimes, the prescription will be to stop androgen deprivation therapy (ADT) for a while or to change the drugs used to deprive the cancer of androgens. Why? In some cases, prostate cancer has mutated so it can use the antiandrogen drug as a stimulant. So, when men are no longer on the antiandrogen drug that had previously worked to contain their cancer, typically, between 15 to 30 per cent of them will experience a drop in prostate-specific antigen (PSA) for a time.  Secondary hormone treatments such as the following might be prescribed when a man’s PSA level begins to rise again:

• If a man has been treated only with drugs that interfere with the production of androgens, second-line hormonal therapy could include the addition of drugs that interfere with the effects of androgens: e.g., flutamide, nilutamide, or bicalutamide.
• Often, a different type of antiandrogen will be effective in controlling the cancer for a while. For example, a man who was treated with flutamide might be asked to stop this drug, wait until his PSA level begins to rise, and then take bicalutamide.
• Another option is to try different sorts of drugs that block the activity of androgens in the body; for example, ketoconazole with or without cortisone-like drugs or estrogens could be used. (Ketoconazole is an antifungal drug with both the potential to kill tumour cells directly and androgen depleting effects.)

New forms of second-line hormone therapy are being developed or refined each month. It would be impossible to list all the drugs or combinations that are currently under trial for use in these treatment regimes, but some of the more studied or promising ones include dutasteride (Avodart), abiraterone,  and the more experimental TAK-700 and MDV3100.

Chemotherapy
If secondary hormone therapy can no longer control a man’s prostate cancer or if a man is diagnosed with castration resistant prostate cancer that has metastasized, chemotherapy may be an option. Until recently, this treatment was considered relatively ineffective for prostate cancer. But new chemotherapy drugs have been developed that both cause PSA levels to drop and prolong life (usually by about 25 per cent compared to men not taking these drugs).

The most significant breakthrough came in 2004, when two studies confirmed that docetaxel (Taxotere®), a chemotherapy drug made from the needles of the European yew tree, improves the survival time and quality of life of men with advanced stage prostate cancer. (See the Network’s article about this discovery.) Currently, the Canadian Urological Association recommends a docetaxel regimen consisting of docetaxel once every three weeks and prednisone taken twice daily. (The docetaxel is given by injection and the prednisone is in pill form.)

Other taxane-based chemotherapy drugs that have been used to fight prostate cancer include paclitaxel and cabazitaxel.  A recent study showed that cabazitaxel and prednisone given to men who had previously been treated with docetaxel for metastatic hormone refractory prostate cancer  “increased survival by 30%.” (See information about this study.)

Immunotherapy and Other Experimental Treatments
Other approaches to controlling hormone resistant prostate cancer are being tested. One initiative uses a cancer vaccine made by isolating white blood cells (dendritic cells) from a patient’s blood and stimulating them outside the body with various chemicals, so they can be re-injecting into the patient to build his immunity against prostate cancer. This vaccine, sipuleucel-T (Provenge®), was approved in 2010 by the U.S. Food and Drug Administration for the treatment of men who have advanced hormone resistant metastatic prostate cancer. (See a PCCN article about this immunotherapy.)

Another immune-based therapy being studied is ipilimumab (MDX-010). And various treatments that target cell-growth mechanisms are also at the testing stage, including mTOR inhibitors and tumour-vascular disrupting agents (e.g., ASA404, vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA). See the article “Treatments and therapies have never been better…” for more on new ways of fighting castration resistant prostate cancer.

Bone-Directed Therapy
Castration resistant prostate cancer frequently spreads or metastasizes to the bone; so many treatment regimes try to delay the progression of metastatic disease in the bone or to destroy bone metastases to relieve pain.

Bisphosphonates such as zoledronic acid (Zometa) are frequently prescribed to alleviate bone pain and stabilize bones weakened by cancer. And they and other medications, such as denosumab, are currently being studied for their potential to delay the spread of prostate cancer that has metastasized to the bone. (See the PCCN article “Prostate cancer and bone health.”)

Spot radiation is also used to alleviate bone pain. But this type of radiation is a palliative therapy, whose purpose is to make a man more comfortable rather than to cure his cancer.


For more information:

Network News special issue on hormone resistant prostate cancer, January 2009

“Treatments and therapies have never been better…”  August 2011

New pathway discovered to possible treatment of advanced prostate cancer, August 2011

Prostate cancer and bone health, June 2011

Abiraterone acetate approved as late-stage prostate cancer treatment, May 2011

“Warriors” spread the word, October 2010

Another step in a new direction: PROVENGE® approved by FDA, May 2010

New drug tested for hormone resistant prostate cancer, April 2009

Battling hormone resistant prostate cancer (ZD4054 and Provenge), July 2007

Taxotere ® : Encouraging news for men with metastatic prostate cancer, December 2005

A ray of hope for men with hormone refractory prostate cancer, August 2004