Prostate cancer – atrasentan
While many forms of cancer have become less of a threat because of increased rates of early diagnosis and improved treatment regimes, prostate cancer remains under-diagnosed, and hence tends not to be treated until the disease is fairly advanced. The cancer is hormone dependent, so the main drugs given as chemotherapy to prostate cancer patients are luteinising hormone releasing hormone agonists and antiandrogens, both of which deprive the tumour of the testosterone it needs to grow.
Another idea being investigated is the use of endothelin antagonists. Endothelins are potent vasoactive agents with several functions in the body. Several forms exist, and one compound under development, atrasentan, is highly selective for the ETA receptors1. It has potential as a treatment for other conditions, including hypertension, but it is also thought that such antagonists could be used in the treatment of advanced cancers.
Atrasentan is being investigated by Abbott Laboratories as a treatment for advanced hormone refractory prostate cancer. Its efficacy and tolerability were investigated in a multi-centre, randomised, placebo controlled, double blind trial in 288 men with hormone refractory prostate cancer who had been either surgically or chemically castrated. Patients treated with the drug showed a substantial delay in time to clinical progression: 184 days on a 2.5mg dose and 196 days with 10mg, compared with 129 days in the group treated with placebo. A significant lowering of bone markers of metastatic progression was also seen. No major side-effects were observed; the drug was largely well tolerated, and the most common side-effects were headache, rhinitis and peripheral oedema2. In another trial on 419 patients, those receiving the placebo showed a much higher increase in these metastatic markers than those receiving atrasentan3.
The compound is undergoing Phase III trials as a potential chemotherapeutic treatment for hormone refractory prostate cancer, and may prove to be a useful addition to the armoury of anticancer drugs.