Living with Prostate Cancer
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The most common types of initial hormone therapy are described in the previous section. These include orchiectomy, LHRH agonists or antagonists, and antiandrogens.
These initial hormone therapies are typically effective for only a few years. After this time, the hormone-independent cells eventually become strong enough that hormone therapies will have less and less of an effect on the growth of the tumor. However, because the hormone sensitive cells aren’t actually eradicated, a number of "secondary" hormone approaches can be used to keep the tumor from spreading.
For many men who were using an antiandrogen in combination with an LHRH agonist, stopping the antiandrogen, or antiandrogen withdrawal, is the most common first step in secondary hormone therapy. About 10-30% of men will experience this anti-androgen withdrawal, which lasts on average 3-5 months, during which time additional therapies are not needed. However, inevitably, additional therapies will be needed even if this withdrawal response occurs. Switching to a different antiandrogen might also be able to offer an extra few months of benefit before other therapeutic approaches are required.
Another option is to block the release of testosterone from the adrenal glands, small organs that sit on top of the kidneys. Only about 10% of the circulating testosterone is produced by these two glands, so few therapeutic interventions focus on them until it becomes important that every last bit of the hormone is removed. The commonly used drugs used for this purpose, ketoconazole and the newer agent abiraterone acetate (Zytiga), are typically administered in conjunction with steroids to avoid the effects seen when the adrenal glands are shut down. Abiraterone acetate plus low-dose steroids has been shown to prolong life when given to men after chemotherapy with docetaxel. A large study evaluating the role of abiraterone acetate prior to chemotherapy has been completed, but the results are not yet available. While awaiting the results of this study, the standard practice is to offer abiraterone treatment after chemotherapy or in men who are not candidates for chemotherapy. Although this medication is generally well-tolerated, side effects may include fatigue, high blood pressure, and electrolyte or liver abnormalities and patients need to be monitored regularly.
In August 2012, the FDA approved enzalutamide (Xtandi) for the treatment of men with castration-resistant metastatic prostate cancer who had disease progression after docetaxel chemotherapy. Similar to but more effectively than the anti-androgens, enzalutamide blocks the androgen receptor. Approval was based on the results of the AFFIRM randomized, phase 3, placebo-controlled trial in which both survival and quality of life were improved with enzalutamide treatment. Side effects are mild but include fatigue, diarrhea, hot flushes, headache, and very rarely seizures. Importantly, enzalutamide treatment does not require simultaneous steroid treatment and therefore the steroid side effects can be avoided. Thus, enzalutamide is a new treatment option for men in the post-docetaxel metastatic CRPC setting and is also a reasonable choice in men who are not candidates for chemotherapy. Evidence to support the use of enzalutamide in the pre-docetaxel setting will be based on the results of the PREVAIL study, which are not yet available.
Side Effects of Hormone Therapy
Testosterone is the primary male hormone, and plays an important role in establishing and maintaining the typical male characteristics, such as body hair growth, muscle mass, sexual desire, and erectile function, and contributes to a host of other normal physiologic processes in the body.
The list of potential effects of testosterone loss is long: hot flashes, decreased sexual desire, loss of bone density and increased fracture risk (osteoporosis), erectile dysfunction, fatigue, increased risk of diabetes and heart attacks/strokes, weight gain, decreased muscle mass, anemia, and memory loss. Cholesterol, especially the LDL cholesterol, tends to rise, and muscle tends to get replaced by fat. Most men who are on hormone therapy experience at least some of these effects, but the degree to which any man will be affected by any one drug regimen is impossible to predict. Before beginning hormone therapy, every man should discuss the effects of testosterone loss with his doctors, so he can alter his lifestyle to accommodate or head off the changes. Exercise is probably the best thing a man can do to prevent many of these side effects.