Many man will require drug treatment for prostate cancer. Some of the drugs lose their effectiveness and need to have additional therapy. This blog will discuss drugs that are used to stop the effect or the production of testosterone which is a necessary hormone for prostate cancer growth.
Drugs that stop androgens from working
Androgens have to bind to a protein in the cell called an androgen receptor in order to work. Anti-androgens stop androgens from working by binding to the receptors so the androgens can’t.
Anti-androgens are not often used by themselves in this country. An anti-androgen may be added to treatment if orchiectomy, an LHRH analog, or LHRH antagonist is no longer working by itself. An anti-androgen is sometimes given for a few weeks when an LHRH analog is first started to prevent a tumor flare.
Anti-androgen treatment may be combined with orchiectomy or LHRH analogs as first-line hormone therapy. This is called combined androgen blockade (CAB). There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH analog alone. If there is a benefit, it appears to be small.
Some doctors are testing the use of anti-androgens instead of orchiectomy or LHRH analogs. Several recent studies have compared the effectiveness of anti-androgens alone with that of LHRH agonists. Most found no difference in survival rates, but a few found anti-androgens to be slightly less effective.
In some men, if hormone therapy including an anti-androgen stops working, the cancer will stop growing for a short time from simply stopping the anti-androgen. Doctors call this the anti-androgen withdrawal effect, although they are not sure why it happens.
This drug is a newer type of anti-androgen. When androgens bind to the androgen receptor, the receptor sends a signal for the cells to grow and divide. Enzalutamide (also known as MDV3100) blocks this signal from the androgen receptor to the cell.
In men with castrate-resistant prostate cancer, enzalutamide can lower PSA levels, shrink or slow the growth of tumors, and help the men live longer.
Enzalutamide is a pill, with the most common dose being 4 pills each day. In studies of this drug, men stayed on LHRH agonist treatment, so it isn’t clear how helpful this drug would be in men with non-castrate levels of testosterone.
Other androgen-suppressing drugs
Estrogens (female hormones) were once the main alternative to orchiectomy for men with advanced prostate cancer. Because of their possible side effects (including blood clots and breast enlargement), estrogens have been largely replaced by LHRH analogs and anti-androgens. Still, estrogens may be tried if androgen deprivation is no longer working.
Ketoconazole (Nizoral®), first used for treating fungal infections, blocks production of certain hormones, including androgens, similarly to abiraterone. It is most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer effective.
Ketoconazole can block the production of cortisol, an important steroid hormone in the body. People treated with ketoconazole often need to take a corticosteroid (like hydrocortisone) to prevent the side effects caused by low cortisol levels.
Possible side effects of hormone therapy
Orchiectomy, LHRH analogs, and LHRH antagonists can all cause similar side effects due to changes in the levels of hormones such as testosterone and estrogen. These side effects can include:
- Reduced or absent libido (sexual desire)
- Impotence (erectile dysfunction)
- Shrinking of testicles and penis
- Hot flashes, which may get better or even go away with time
- Breast tenderness and growth of breast tissue
- Osteoporosis (bone thinning), which can lead to broken bones
- Anemia (low red blood cell counts)
- Decreased mental sharpness
- Loss of muscle mass
- Weight gain
- Increased cholesterol
Anti-androgens have similar side effects. The major difference from LHRH agonists and orchiectomy is that anti-androgens may have fewer sexual side effects. When these drugs are used alone, libido and potency can often be maintained. When these drugs are given to men already being treated with LHRH agonists, diarrhea is the major side effect. Nausea, liver problems, and tiredness can also occur.
Abiraterone does not usually cause major side effects, although it can cause joint or muscle pain, high blood pressure, fluid buildup in the body, hot flashes, upset stomach, and diarrhea.
Enzalutamide can cause diarrhea, fatigue, and worsening of hot flashes. This drug can also cause some neurologic side effects, including dizziness and, rarely, seizures. Men taking this drug are more likely to have problems with falls, which may lead to injuries.
Many side effects of hormone therapy can be prevented or treated. For example:
- Hot flashes can often be helped by treatment with certain antidepressants or other drugs.
- Brief radiation treatment to the breasts can help prevent their enlargement, but it is not effective once breast enlargement has occurred.
- Several different drugs are available to help prevent and treat osteoporosis.
- Depression can be treated by antidepressants and/or counseling.
- Exercise can help reduce many side effects, including fatigue, weight gain, and the loss of bone and muscle mass.
There is growing concern that hormone therapy for prostate cancer may lead to problems with thinking, concentration, and/or memory. But this has not been studied well in men getting hormone therapy for prostate cancer. Studying the possible effects of hormone therapy on brain function is hard, because other factors may also change the way the brain works. A study has to take all of these factors into account. For example, both prostate cancer and memory problems become more common as men get older. Hormone therapy can also lead to anemia, fatigue, and depression – all of which can affect brain function. Still, hormone therapy does seem to lead to memory problems in some men. These problems are rarely severe, and most often affect only some types of memory. More studies are being done to look at this issue.
Bottom line: Many man experience recurrence of their prostate cancer after treatment. Hormone therapy is the most common treatment option for men in this situation.