What are the treatment options for castration-resistant prostate cancer? 


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Treatments for castration-resistant prostate cancer include:

  • Antiandrogens, such as flutamide, bicalutamide, nilutamide, and enzalutamide
  • Androgen synthesis inhibitors, such as ketoconazole, aminoglutethamide, and abiraterone acetate
  • Immunotherapy using a cell-based vaccine called sipuleucel-T. This vaccine uses a man’s own immune cells to fight metastatic prostate cancer that has become resistant to hormone therapy.
  • Chemotherapy, most commonly with the drug docetaxel. Another drug, cabazitaxel, is approved for the treatment of metastatic castration-resistant prostate cancer that was previously treated with docetaxel.
  • Radium 223 dichloride, a radiopharmaceutical approved to treat men with castration-resistant prostate cancer that has metastasized (spread) to the bones and is causing symptoms but has not spread to other organs. This drug collects in certain areas of bone, such as bone metastases, and gives off radiation that kills cancer cells.

Men with castration-resistant prostate cancer who receive these treatments will continue to take first-line hormone therapy (e.g., an LHRH agonist) to avoid an increase in testosterone level, which may lead to tumor progression in some men.14

Randomized clinical trials have demonstrated that treatment with abiraterone acetate or enzalutamide prolongs survival among men with metastatic castration-resistant prostate cancer, whether or not they have previously received chemotherapy.15,18

What are the side effects of hormone therapy for prostate cancer?

Both medical castration and surgical castration greatly reduce the amount of androgens produced by the body. Because androgens are used by many other organs besides the prostate, medical or surgical castration can have a wide range of side effects3,19:

  • Loss of interest in sex (lowered libido)
  • Erectile dysfunction
  • Hot flashes
  • Loss of bone density
  • Bone fractures
  • Loss of muscle mass and physical strength
  • Changes in blood lipids
  • Insulin resistance
  • Weight gain
  • Mood swings
  • Fatigue
  • Growth of breast tissue (gynecomastia)

Antiandrogens can cause diarrhea, breast tenderness, nausea, hot flashes, loss of libido, and erectile dysfunction. The antiandrogen flutamide may damage the liver.

Drugs that stop the adrenal glands from making androgens (i.e., the androgen synthesis inhibitors ketoconazole, aminoglutethimide, and abiraterone acetate) can cause diarrhea, itching and rashes, fatigue, erectile dysfunction (with long-term use), and, potentially, liver damage.

Estrogens avoid the bone loss seen with other kinds of hormone therapy, but they increase the risk of cardiovascular side effects, including heart attacks and strokes. Because of these side effects, estrogens are rarely used today as hormone therapy for prostate cancer.

Having adjuvant hormone therapy after radiation therapy worsens some adverse effects of radiotherapy, particularly sexual side effects and vitality.20 Many of the side effects of ongoing hormone therapy also become stronger the longer a man takes hormone therapy.19

What can be done to reduce the side effects of hormone therapy for prostate cancer? 

Men who lose bone mass during long-term hormone therapy may be prescribed drugs to slow or reverse this loss. The drugs zoledronic acid and alendronate (which belong to a class of drugs called bisphosphonates) increase bone mineral density in men who are undergoing hormone therapy.21,22 A newer drug, denosumab, which increases bone mass through a different mechanism than bisphosphonates23, was approved in 2011 for use in men undergoing hormone therapy for prostate cancer. However, bisphosphonates and denosumab are associated with a rare but serious side effect called osteonecrosis of the jaw.14

Exercise may help reduce some of the side effects of hormone therapy, including bone loss, muscle loss, weight gain, fatigue, and insulin resistance.14,24 Several clinical trials are examining whether exercise is an effective strategy to reverse or prevent side effects of hormone therapy for prostate cancer.

The sexual side effects of hormone therapy for prostate cancer can be some of the most difficult to deal with. Erectile dysfunction drugs such as sildenafil citrate (Viagra®) do not usually work for men undergoing hormone therapy because these drugs do not affect loss of libido (sexual desire).

When most men stop taking a reversible hormone therapy, the sexual and emotional side effects caused by low levels of androgens will eventually go away. However, if a man has been taking hormone therapy for many years, these side effects may not disappear completely. Some physical changes that have developed over time, such as bone loss, will remain after stopping hormone therapy.

Patients should be sure to tell their doctor about all medications they are taking, including over-the-counter herbal medicines. Some herbal medicines interact with drug-metabolizing enzymes in the body, which can adversely affect hormone therapy.25

Does a reversible hormone therapy have to be taken continuously for it to be effective?

Researchers have investigated whether a technique called intermittent androgen deprivation can improve the effectiveness of hormone therapy for prostate cancer—that is, whether it delays the development of hormone resistance. With intermittent androgen deprivation, hormone therapy is given in cycles, with breaks between drug administrations, rather than continuously. An additional potential benefit of this approach is that the temporary break from the side effects of hormone therapy may improve a man’s quality of life.

Two clinical trials of intermittent versus continuous androgen deprivation found that intermittent therapy reduced some of the side effects of hormone therapy, including those involving sexual function. However, the trials did not show any improvement in overall survival with intermittent therapy.26,27