Androgen Deprivation Therapy (ADT) is usually recommended first for men with advanced or metastatic prostate cancer.
What Is Androgen Deprivation Therapy?
Male hormones (androgens, the most common of which is testosterone) fuel the growth of prostate cancer. Treatments that decrease the body's levels of androgens, or ADT, decrease the size of prostate cancer. ADT can be done by taking medicines that interfere with androgens, or by having surgery to remove the testicles (called an orchiectomy). In Canada, medical treatment is usually preferred to surgery for advanced disease.
Examples of the medicines used in ADT include:
- GnRH agonists - GnRH agonists are medicines that temporarily "turn off" the testicles' production of male hormones (androgens). This starves the cancer cells, causing the prostate to shrink. GnRH agonists are given as a shot every three to six months and include leuprolide (Lupron) and goserelin (Zoladex).
- Combined androgen blockade (CAB) - Some doctors recommend a second medicine, called an antiandrogen, in addition to the GnRH agonist. Examples of antiandrogens include flutamide (Eulexin), enzalutamide (Xtandi) and bicalutamide (Casodex).
Side Effects Of Androgen Deprivation Therapy
The side effects of ADT are related to the lowered levels of male hormones and include:
- Decreased libido (sex drive), and difficulties with erection (erectile dysfunction)
- Hot flashes
- Enlargement of the breasts (called gynecomastia)
- Loss of muscle and an increase in body fat
- Thinning and weakening of the bones (called osteoporosis), which can increase the risk of bone fractures
- An increased risk of developing type 2 diabetes
- An increased risk of developing or worsening coronary heart disease, which can lead to heart attack
Many of these side effects are serious and might seem frightening. Not all men have these side effects. It is important to balance the risk of side effects with the risk of not using androgen deprivation, which could allow your cancer to grow or spread. In most men, the risk of the cancer growing or spreading outweighs the possible risk of side effects. In addition, there are ways to prevent or treat many of these side effects.
When To Start Androgen Deprivation Therapy?
Experts disagree about the best time to start ADT. Many doctors recommend starting it when metastatic prostate cancer is first diagnosed; the hope is that treatment will slow the growth of the cancer, and possibly prolong survival. Others believe that early ADT is not curative and can cause bothersome side effects. Doctors in this group recommend delaying the start of treatment until symptoms of cancer (like bone pain) develop. Discuss the benefits and risks of each approach with your doctor.
Secondary Hormone Therapy
Most men with advanced prostate cancer initially respond well to ADT, but then prostate cancer comes back within two years. At this point, the cancer is termed androgen resistant, meaning that ADT alone is no longer effective. Once this occurs, secondary hormone therapy is usually considered. Even when prostate cancer becomes androgen resistant, some form of ADT is usually continued because at least a portion of the cancer cells might still respond.
Secondary Hormone Therapy can include:
- Stopping the antiandrogen (flutamide, nilutamide, bicalutamide)
- Trying a different type of antiandrogen. Cancer that is resistant to one antiandrogen treatment may not be resistant to another.
- Trying another medicine that blocks the activity of androgen in the body, including estrogen, steroids, or the antifungal medication ketoconazole.
Eventually, most men with advanced prostate cancer stop responding to all forms of hormone treatment. This is called castrate-resistant prostate cancer (CRPC). The next step in treatment often includes chemotherapy.
Chemotherapy is a treatment given to slow, or stop, the growth of cancer cells. Most treatments involve a combination of several chemotherapy drugs (called regimens). Most of the drugs are given into the vein (intravenous, IV).
Chemotherapy is not given every day, but instead is given in cycles. A cycle of chemotherapy (which is typically 21 or 28 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines.
Side effects of chemotherapy can include:
- Temporary hair loss
- Nausea and vomiting
- Lowered blood counts, which increase the risk of developing an infection.
Bone Pain Treatment
The bones are a common place for prostate cancer to spread. Androgen deprivation therapy can often control the cancer that has spread to bones.
Men who develop bone pain in one or a few bones as a result of the cancer can be treated with Radiation Therapy to relieve their pain. The radiation is usually given in one or a few visits, similar to having an X-ray. Some people have worsened pain for one to two days immediately after the radiation treatment; however, most people feel partial or complete improvement of pain within a week after treatment.
Emerging Therapies For Treatment Of Castrate-Resistant Prostate Cancer (CRPC)
There are a number of new avenues being explored for the treatment of CRPC, including:
- The Androgen Receptor (AR) axis
CRPC tumours develop compensatory mechanisms during androgen starvation which re-activate the AR and lead to disease progression.
CRPC's are not uniformly hormone refractory, and may remain sensitive to therapies directed against the AR axis. Tumours should not be termed “hormone resistant” or “hormone refractory”.
Angiogenesis is the process by which the body generates new blood vessels. New blood vessels are necessary if tumors are to grow and metastasize and are associated with disease progression and a poor prognosis. Inhibiting angiogenesis has been shown to be effective in a number of cancer types. Several anti-angiogenic agents are in late stage trials in CRPC; however, negative results from bevacizumab plus docetaxel reduces likelihood of success of this class.
- ET -1 Receptor
Endothelin-1 is produced by prostate epithelia and plays an important role in prostate cancer. Activation of the Endothelin Type A (ETA) receptor by ET-1 promotes cell proliferation and survival ETA blockade has significant effects in CRPC. ETA blockade may have additive ant-tumor effects when used in conjunction with other chemotherapeutics.
- Molecular Chaperones
Chaperones are essential to the viability of cells and act as genetic buffers stabilizing the cells to environmental stress such as heat or toxic chemicals (such as chemotherapeutic agents). Molecular Chaperones have several functions which inhibit treatment-induced cell death. Targeting those with roles associated with cancer progression and treatment resistance is an attractive therapeutic strategy as an addition to conventional chemotherapy.
- Immune Therapies
Aim to stimulate the immune system to reject or destroy tumours. Promising results have been reported with the cancer vaccine Provenge, and was recently approved by the U.S. Food and Drug Administration (FDA).