Hormonal therapy for advanced prostate cancer
Hormonal therapy is the main treatment for men with advanced prostate cancer. It can shrink the cancer, delay its growth, and reduce symptoms.
Prostate cancer depends on the hormone testosterone in order to grow. Testosterone is produced by the testicles and a small amount is also produced by the adrenal glands. Hormonal therapies work by reducing the amount or activity of testosterone in the body.
There are different types of hormonal therapies that can be used to treat advanced prostate cancer. You may be offered treatment with more than one type. If you’ve had hormone treatment before, you may be advised to try a different type.
Hormonal therapies can be given as injections or tablets. Occasionally, an operation called a subcapsular orchidectomy may be done to remove the part of the testicles that produces testosterone.
Hormonal treatment works well for most men with advanced prostate cancer, and the cancer can often be controlled for some time. Your doctor will check how well the cancer is responding to treatment by checking your symptoms and examining you. Your PSA level will also be measured, as this is usually a good guide to how effective treatment is. If the cancer starts to grow again, your doctor may suggest you change to a different hormonal therapy drug.
Although there are several drugs that can be used, at some point the cancer will stop responding to hormonal therapy. This is known as hormone-refractory prostate cancer or castration-refractory prostate cancer. If hormonal therapy is no longer working, your doctor may suggest chemotherapy or other treatments to relieve symptoms (palliative treatments).
Hormonal therapy injections
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GnRH agonists (pituitary down-regulators)
This type of hormonal therapy ‘switches off’ the production of testosterone by the testicles in an indirect way.
The pituitary gland is a gland in the brain that produces hormones that control and regulate the other glands in the body. Gonadotrophin-releasing hormone (GnRH) is a hormone that stimulates the pituitary gland to produce a hormone called luteinising hormone (LH), which stimulates the testicles to make testosterone.
GnRH agonists reduce the levels of LH produced by the pituitary gland, and this in turn lowers the level of testosterone. These drugs are also called pituitary down-regulators.
There may be a temporary increase in testosterone levels for the first few days of treatment, which may increase your symptoms. This is known as tumour flare and is normal. Your doctor may prescribe an anti-androgen tablet ( see below ) to prevent this. If you have any problems, let your doctor know.
Examples of this type of hormonal therapy are:
These are usually given as a pellet (goserelin) injected under the skin of the tummy (abdomen), or as a liquid (leuprorelin or triptorelin) injected under the skin or into a muscle. Injections are usually given either monthly or every three months.
Another GnRH agonist called Vantas® (histrelin acetate) may sometimes be used to treat advanced prostate cancer. It’s given just once a year as an implant under the skin. It’s approved for use in the NHS in Scotland by the SMC (Scottish Medicines Consortium). However, it is not widely available on the NHS in England, Wales and Northern Ireland.
This type of hormonal therapy stops the production of luteinising hormone by the pituitary gland and so reduces the level of testosterone produced by the testicles. The cancer cells then grow more slowly or stop growing altogether, and the cancer may shrink in size. GnRH antagonists works much more quickly than GnRH agonists and don’t cause tumour flare.
Degarelix (Firmagon®) is a GnRH antagonist. It’s usually given as a liquid injected under the skin of the tummy every month.
Hormonal therapy tablets (anti-androgens)
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Some hormonal therapy drugs work by attaching themselves to proteins (receptors) in the cancer cells. This blocks the testosterone from acting on the cancer cells. These drugs are called anti-androgens and are given as tablets. Commonly used anti-androgens are:
Anti-androgen tablets can be used alone as hormonal treatment for prostate cancer, but they can also be used before treatment with a pituitary down-regulator (GnRH agonist) starts. This prevents tumour flare. The tablets are usually started two weeks before starting with the pituitary down-regulator and continued for a week after you’ve had the injection.
Anti-androgen withdrawal response
If hormonal therapy with an anti-androgen drug has been given for some months or years and the cancer begins to grow again, stopping the anti-androgen drug may make the cancer shrink for a while. This is known as an anti-androgen withdrawal response and occurs in up to one in four men (25%) who stop anti-androgen therapy.
Intermittent hormonal therapy
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The side effects of hormonal therapy can influence the quality of life for some men. Intermittent hormonal therapy aims to improve this. If you have very bad side effects from hormonal therapy, your doctors may stop your treatment temporarily once you have responded to treatment. This is to reduce the side effects. Once the disease has started to progress again, hormonal therapy is re-started.
Your PSA levels will be monitored during the time you aren’t having treatment. The outcome of this approach to treatment is still being researched. Your doctor can discuss the advantages and disadvantages of it with you.
Side effects of hormonal therapy
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Unfortunately, most hormonal therapies can cause erection difficulties (impotence) and loss of sexual desire (libido) for as long as the treatment is given. If the treatment is stopped, the problem may resolve. Some anti-androgens are less likely to cause impotence than others.
In some men who have hormonal therapies, the side effects that cause the greatest problems are hot flushes and sweating. These stop if the treatment is stopped and the testosterone levels recover. There are medicines that can help with these side effects – we can send you information about these.
Hormonal treatment can also make you put on weight and feel tired, both physically and mentally. Some drugs (most commonly flutamide and bicalutamide when given on their own) may also cause your breasts to swell and feel tender. Your doctors may advise a short course of low-dose radiotherapy to your breasts before you start the drugs to try to prevent swelling. If breast swelling does occur, a tablet called tamoxifen may help to ease this.
Different drugs have different side effects, so it’s important to discuss these with your doctor before you start treatment. Being aware of the possible side effects can make them easier to cope with.
Advantages and disadvantages of hormonal therapy
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Hormonal therapy can shrink the cancer, delay its growth and relieve symptoms for many months or years.
Hormonal therapy can cause a range of side effects that include breast swelling, hot flushes, weight gain, fatigue, difficulty getting and maintaining an erection (impotence) and a lowered sex drive (libido).
Subcapsular orchidectomy (removal of part of the testicles)
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This is an operation to remove the part of the testicles that produces testosterone. A small cut is made in the scrotum (the sac that holds the testicles) , and the part of the testicles that produces testosterone is removed. After the operation the scrotum will appear smaller than it was before.
The operation can be done under a local anaesthetic without the need to stay in hospital overnight. Sometimes both testicles are completely removed (bilateral orchidectomy).
Some men find the idea of this operation distressing. You may find it helpful to talk through the procedure with your cancer specialist, who can give you more information about what this operation involves.
After the operation, you’ll have some pain, and swelling and bruising of the scrotum. Other side effects that develop later are similar to those of hormonal therapy drugs, which include hot flushes and impotence.
Advantages and disadvantages
A subcapsular orchidectomy is a simple operation that avoids the use of drugs and some of the associated side effects such as breast swelling and tenderness. Subcapsular orchidectomy and other hormonal treatments are equally effective.
Some men find the idea of this operation difficult to cope with. As with any operation, there are risks associated with surgery. Your cancer specialist will give you more information about these risks and the side effects you’re likely to have.
Other hormonal treatments
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Once the cancer is no longer responding to GnRH agonists, GnRH antagonists or anti-androgens, many men can have further periods of remission and a good quality of life by taking either diethylstilbestrol (Stilboestrol®) or steroids .
Stilboestrol is a man-made drug that’s very similar to the female hormone oestrogen. It reduces the amount of testosterone in the body and is taken as a tablet once a day.
Side effects include loss of sex drive, loss of facial hair, and it may also cause some breast tenderness and swelling. Stilboestrol can also increase the risk of getting a blood clot (deep vein thrombosis). Your doctor may prescribe drugs called warfarin or aspirin to reduce the risk of blood clots.
Sometimes a drug called ethinylestradiol is used instead of Stilboestrol. The side effects are similar to those of Stilboestrol.
Steroids called prednisolone or dexamethasone are also taken as tablets. They may cause some weight gain and increase in appetite, but are usually tolerated well. Sometimes steroids may be given with chemotherapy. Occasionally, they can cause mood swings, difficulty sleeping and irritability. Let your doctor know if you get any of these side effects. Difficulty sleeping may be helped by taking the steroids earlier in the day, but check this with your doctor first.
A new type of hormonal therapy called abiraterone acetate is also available. It may be used in men when other types of hormonal therapy and docetaxel chemotherapy are no longer working. Abiraterone has some side effects including a high blood pressure and tiredness. Your doctor will be able to give you more information about this.
The National Institute for Health and Clinical Excellence (NICE) gives advice on which new drugs or treatments should be available on the NHS in England and Wales. The Scottish Medicines Consortium (SMC) is an organisation similar to NICE for the NHS in Scotland. Abiraterone is recommended for use by NICE and the SMC.