Prostate disease and the pharmaceutical industry

Prostate Cancer

Medicines that stop testosterone action

Around 5 to 10 per cent of the testosterone in the blood is released from the adrenal gland after ACTH stimulation. This testosterone is still produced even when LHRH agonists are used and may be enough to stimulate growth of the cancer. Hence, medicines have been developed that stop this circulating testosterone from binding to the cancer cell testosterone receptors. These are called antiandrogens (an androgen is a male hormone of which testosterone is the most abundant). Two antiandrogens are currently available in the UK – flutamide (Schering Plough) and bicalutamide (AstraZeneca).

Antiandrogens can be used on their own. Clinical trials with flutamide suggested that it may not suppress sexual desire or cause impotence, and can be of great value, especially in younger men with prostate cancer who wish to remain sexually active. Clinical trials with bicalutamide as a single medication have shown that sexual interest is still maintained when compared to surgical removal of the testes. Antiandrogens are not, however, entirely free of side effects and can cause breast tenderness and gastric disturbances.

More often though, antiandrogens are given in combination with an LHRH agonist, a strategy called maximum androgen blockade. The antiandrogens are started a few days before the LHRH analogue, to ensure that the testosterone receptors are blocked against the testosterone flare. Clinical trial results with combinations have been variable, but studies with leuprorelin combined with flutamide or bicalutamide showed that maximum androgen blockade increases the time to disease progression and increases survival in men who are fitter at the outset.

A third antiandrogen is cyproterone acetate (Schering Health Care). It is prescribed less today because, unlike bicalutamide and flutamide, it is related to the female sex hormone progesterone. It has similar effects to the non-steroidal antiandrogens, namely to reduce testosterone and block its action on the prostate. It can help control the hot flushes experienced by some men on LHRH agonists and reduces the flare in testosterone seen at the beginning of LHRH agonist treatment, but it does have some side effects.

Antiandrogens may be given in addition to surgical removal of the testes, again with beneficial results. Trials reported in May 2000 also showed that the LHRH agonist, goserelin, together with external beam radiotherapy, reduced the number of disease recurrences and improved survival.