Hormone therapy is the accepted first treatment when cancer has spread beyond the prostate. It is also often used should the cancer return. It can also be used temporarily to shrink the cancer prior to some forms of treatment for localised prostate cancer.
In order to grow, most prostate cancers need the male hormones (androgens), the most common of which is testosterone. By inhibiting the generation of testosterone, the cancer will be starved and shrink. This treatment is often used when the prostate cancer has spread beyond the prostate, or has recurred after other types of treatment. It is also used in combination with radiotherapy in order to shrink the tumour so that the radiotherapy can be more effective.
Hormone treatment alone does not cure the cancer but may control it for 2 –10+ years before the cancer becomes hormone resistant (now sometimes referred to by the medical profession as ‘castration resistant’) i.e. when it no longer responds to first-line hormone therapy. This is indicated by a rise in PSA level. A marked lowering of the PSA is usually a good indication of the effectiveness of hormone treatment.
There are several methods used for hormone treatment. These are:
Orchidectomy is the surgical removal of the testicles. This is where most testosterone is produced, (though a small amount is also produced in the adrenal glands). This treatment is effective, but understandably is not favoured by most patients and is rarely performed nowadays.
This is short for Luteinising Hormone-Releasing Hormone. These drugs can decrease the amount of testosterone produced by the testicles as effectively as surgical removal. Two common examples of these drugs are Zoladex (Goserelin) and Prostap (Leuprorelin). They are administered by the injection of a slowly dissolving pellet either monthly, three monthly or once a year. Less common is Histrelin (Vantas), administered by a soft implant just under the skin at the top of the arm. Triptorelin (Decapeptyl or Gonapeptyl) is another drug that can be used, especially in cases of aggressive advanced prostate cancer. When first administered, these drugs cause an initial surge of testosterone, which is counteracted by a short course of anti-androgen tablets shortly before and after the first injection.
These drugs do not stop the production of testosterone but block the effects of both testicular and adrenal androgens. Two common examples of these drugs are Cyprostat (Cyproterone acetate) and Casodex (Bicalutamide). They are usually taken in pill form, which makes them attractive to those who do not like the thought of regular injections. Anti-androgens can be used as a stand-alone therapy (referred to as ‘anti-androgen monotherapy’), or can be used in combination with LH-RH analogues, referred to as ‘maximum (or total) androgen blockade’. Some men may prefer anti-androgens because of the reduced side effects, but evidence shows that they are not quite as effective as LH-RH analogues.
Intermittent hormone therapy is a process in which the hormone treatment is started and stopped for periods while monitoring the PSA. When the PSA rises, treatment is restarted. The object of this process is to reduce the side effects of the treatment and, hopefully, to extend the period for which this treatment is effective. Some trials have shown that intermittent treatment can be as effective as continuous treatment, and with less side effects.
When the ‘first line’ hormone drugs referred to above lose their effectiveness, there are other drugs which have been shown to work, although only for a limited period of time. These include steroids such as Dexamethasone, which stops the adrenal glands from producing other male hormones. These ‘second line’ drugs are often used in combination with the ‘first line’ hormone drugs.
Oestrogen therapy is another form of treatment. The main oestrogen for prostate cancer is Stilboestrol (an abbreviation of ‘diethylstilboestrol’).
This is a synthetic female hormone which suppresses the effects of testosterone. Treatment is generally given in the form of daily tablets.
Common side effects of both kinds of hormone therapy are hot flushes for short periods, which can occur at night, affecting sleep, for which a short course of low-dose anti-androgens may be prescribed. Eliminating alcohol, tea and coffee (or using decaffeinated drinks) and going on a soya diet (to replace milk) may also help. Weight gain, bone or muscle pain, joint pain, numbness and tingling in hands and feet, and possible hair loss on face, arms, legs or underarm are other listed side effects. Some may find these hard to live with, but with time many will reduce in severity as the body adjusts. Therapies or medication can, of course, be changed should these become a problem.
LH-RH analogue side effects. The main side effect is that the patient will be impotent and lose his sex drive; but unlike orchidectomy the process is gradually reversed if the patient stops taking the drug. Some men may suffer from decreased size of testicles and some slight penile shrinkage. Initially these drugs can produce a flare in testosterone, which settles after a few weeks.
Anti-androgen side effects. A common side effect of these drugs is tender or enlarged breast tissue (gynaecomastia), which may subside if treatment is ceased. Low doses of Tamoxifen (an anti-oestrogen) can reduce this side effect. Other possible concerns may be nausea, diarrhoea, itching, feeling weak, and problems with the liver. As the drugs affect your hormone levels, this may cause some anxiety or depression. Although there is still a risk of impotence and other adverse sexual side effects with antiandrogens, these are less severe than with LH-RH analogues (or with orchidectomy, where it is permanent).
Oestrogen therapy side effects. This carries an increased risk of blood clotting. Like the other drugs, side effects include breast enlargement and tenderness, erectile problems and mood changes. Other listed side effects are less common, and many men will experience only a few of these. It is reported that oestrogen patches on the skin may produce fewer side effects.
There are two new drugs that may be able to prolong the time before the standard hormone treatments cease to be effective (i.e. when the disease becomes hormone refractory), or for use after chemotherapy treatment. They are:
Abiraterone Acetate (Zytiga). This is an androgen-synthesis inhibitor that has done well for many patients with advanced cancers that have become resistant to hormone treatments. Abiraterone has at last been authorised for use in the NHS as a treatment after chemotherapy, but not as a second-line treatment when standard hormone drugs begin to fail. It is highly effective in improving survival of some types of prostate cancer, but not all.
MDV3100 (Enzalutamide) is an advanced anti-androgen that is showing outstanding results, but its use has yet to be approved. (See ‘Trials’ on page 40 for more details of this and other drugs that may be in the pipeline.)