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Drugs for prostate cancer

MagazineMay 2005 (Vol. 16 Issue 2)Drugs for prostate cancer

Hot flushes, loss of libido, weight gain - sound familiar? For our female readers who are currently in, or have already gone through, menopause, the answer is probably a resounding 'yes'

Hot flushes, loss of libido, weight gain - sound familiar? For our female readers who are currently in, or have already gone through, menopause, the answer is probably a resounding 'yes'. However, these symptoms are not exclusive to women undergoing the change. They also belong to a long list of side-effects linked to androgen-deprivation therapy (ADT), a hormone therapy increasingly being prescribed to men with prostate cancer.

The latest evidence shows that up to one-fifth of patients experience a crippling variety of osteoporosis with this supposedly safer alternative to prostate surgery - quadrupling their risk of a fractured spine.

Unlike other cancer treatment options such as chemotherapy, ADT doesn't kill cancer cells. Instead, it stops the tumour from spreading by decreasing the production of male hormones such as testosterone, which stimulate prostate cancer cells, causing them to grow.

But messing about with hormones is never a good thing, and creating an imbalance in our delicate hormonal system can only open up a Pandora's box of adverse effects.

The true cost of treatment
Loss of bone density (osteoporosis) is a well-recognised side-effect of ADT, and an increasing body of evidence is bringing to light the significance of this symptom. One study, published earlier this year in the New England Journal of Medicine, investigated the incidence of fracture risk after ADT for prostate cancer. The results showed that 19.4 per cent of those who received ADT suffered a fracture, a significantly greater number of casualties compared with the 12.6 per cent in the group not taking ADT (N Engl J Med, 2005; 352: 154-64).

More evidence has also recently emerged from a Spanish study that found that patients receiving ADT were four times more likely to experience fractures of the spine, wrists and ankles (Osteoporos Int, 2005; Feb 16 [e-pub ahead of print]).

Obesity, abnormally high blood sugar and anaemia are also common findings with ADT, putting patients at an increased risk of developing other serious, non-cancer health problems such as cardiovascular disease and diabetes.

Some side-effects of ADT may not have life-threatening consequences, but can cause a debilitating downturn in quality of life. These include a decreased libido and impotence, experienced by nearly 90 per cent of men undergoing ADT; hot flashes, seen in more than 50 per cent of cases; fatigue; mood swings; breast enlargement; decreased strength from loss of muscle mass; and depression - though this could be due to the other side-effects or to other cancer-related issues and not the treatment itself.

Although the side-effects are similar across the different forms of ADT, each type of treatment does bring its own characteristic complications.

ADT in its various guises
Orchiectomy, more commonly known as 'castration', is the oldest form of ADT. This involves surgically removing the testes, where over 90 per cent of testosterone is produced. Given the significant psychological trauma following such surgery (regret is a common reaction) and its irreversibility, drugs are now the preferred means of hormone control.

Luteinising hormone-releasing hormone (LHRH) analogues, such as Zoladex and Lupron, are the mainstay of ADT. Patients receive regular injections every three, four, six or 12 months, and usually for the rest of their life. This makes it costlier than surgery, but it is reversible.

These drugs mimic the testosterone-regulating hormones made in the brain. Testosterone production increases during the first one or two weeks - causing a tumour flare-up - before decreasing to the desired low levels.

While the tumour flare-up is only temporary, it can lead to serious bone pain in men whose prostate cancer has spread to the bones. If the cancer has reached the spine, an increase in growth could cause the tumour to press against the spinal cord, causing intense pain and even paralysis.

As is the way of the pharmaceutical industry, a newer drug has been recently introduced to overcome the problem of tumour flare. Plenaxis is an LHRH antagonist with the alleged advantage of reducing testosterone more quickly and without the tumour growth spurt. However, there were reports of severe allergic reactions to the drug in the clinical trials (Drugs R&D, 2003; 4: 161-6; Eur Urol, 2004; 46: 279-83; 283-4). As a result, the drug is only approved for use in men who have serious symptoms due to advanced prostate cancer and who cannot take any other forms of ADT.

And despite being a new-generation, 'bigger-and-better' drug, patients are warned that Plenaxis may become less effective over time - which means that, after enduring the side-effects, you're soon back to square one.

Another class of drugs used in ADT are antiandrogens (Casodex, Eulexin, Nilandron). As the name suggests, these drugs - taken daily as pills - block the body's ability to use not just testosterone, but any type of androgen.

There is still debate over whether antiandrogens provide a more effective treatment than the LHRH analogues. Some side-effects associated with LHRH analogues are either not seen with antiandrogens (no tumour flare) or are less severe (fewer reports of impotence). However, diarrhoea, with possible rectal bleeding and inflammation, is a significant side-effect of Eulexin, and Nilandron can impair night vision in some men. Patients taking antiandrogens also run the risk of developing liver damage, though impotence appears less often than with other forms of hormone therapy.

Tina Tan


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