Prostate cancer drug breakthrough for aggressive form of disease


Prostate cancer drug breakthrough for aggressive form of disease

A new trial drug called abiraterone has shown a high success rate at treating men with an aggressive, drug resistant, and often fatal form of prostate cancer. 70 to 80 per cent of the men on the trial experienced dramatic reductions in PSA (a protein marker for prostate cancer) and tumour shrinkage, even in tumours that had spread to bone and other tissue.

The study, which is published in the 21st July online issue of the Journal of Clinical Oncology, was the work of researchers based at the Institute of Cancer Research (where the drug was discovered) and The Royal Marsden Hospital in London, and funded by Cougar Biotechnology, Inc of Los Angeles, California.

The results of the Phase 1 clinical trial suggest that abiraterone could treat up to 10,000 British men diagnosed each year with the aggressive and often fatal form of prostate cancer.

Lead investigator on the trial, Dr Johann de Bono, of the Institute of Cancer Research in Sutton, Surrey, UK, said the drug worked by blocking hormones that drive the growth of prostate cancer tumours.

"Clinical benefits included evidence of PSA falls and tumour shrinkage which was observed in 70-80 per cent of patients," said de Bono, explaining that they used CAT, MRI and bone scans, as well as blood levels of PSA to measure tumour shrinkage.

"Abiraterone works not only in blocking the generation of these hormones in the testes, but also elsewhere in the body, including generation of hormones in the cancer itself," he added.

All the patients on the trial had an aggressive form of prostate cancer whose tumours were thought to be producing their own supply of hormones, which may explain why treatment with drugs that only block hormones produced by the testes did not work.

The researchers decided to carry out the study because up to that point, studies on what is called castration-resistant prostate cancer (CRPC) showed that the tumours were still being driven by supplies of the male hormone androgen. They decided to trial abiraterone because it is a precision drug that targets a specific enzyme that plays a key role in the synthesis of androgen, called cytochrome P (CYP) 17.

For the trial, they enrolled 21 men who had prostate cancer that was resistant to multiple hormonal therapies; none of them had received chemotherapy. The men were split into three groups, and given an escalating daily dose of the drug (starting at 250 and finishing with 2,000 mg).

The results showed that:

  • Abiraterone acetate was well tolerated.
  • Anticipated side effects such as high blood pressure, low potassium and swelling in the lower limbs were successfully managed with other drugs (mineralocorticoid receptor antagonist to balance the effect of secondary mineralocorticoid excess).
  • Anti tumour effects were observed in all doses, but because the effect appeared to level off at 1,000 mg, this was selected as the dose for expanding the trial to include another 9 patients.
  • PSA (prostate specific antigen) levels went down by 30 per cent in 14 patients (66 per cent of the participants), by 50 per cent in 12 patients (57 per cent of participants) and 90 per cent in 6 patients (29 per cent of participants) and lasted between 69 to 578 days or more.
De Bono and colleagues concluded that:

"CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC." They also said that these findings confirm that this type of prostate cancer (CRPC) depends on signalling by the androgen hormone.

"The Royal Marsden patients in this study have been monitored for up to two-and-a-half years and with continued use of abiraterone they were able to control their disease with few side-effects. A number of patients were able to stop taking morphine for the relief of bone pain," said de Bono.

"We hope that abiraterone will eventually offer them real hope of an effective way of managing their condition and prolonging their lives," he said, estimating that the drug should be available for general use from 2011. Until then it will only be available to patients on clinical trials.

Prostate cancer is the most common cancer among men in the UK, where 35,000 new cases are diagnosed and 10,000 men die of the disease every year, nearly all from the CRPC form.

One patient on the trial, Robin Wood, 65, who lives in Wokingham, near Reading, was diagnosed with an aggressive drug resistant form of prostate cancer in May 2007. He said in a statement from the Institute of Cancer Research that:

"My prostate was very cancerous and I had only a one in five chance of being alive by the end of 2008."

"However, abiraterone radically changed that, with my health improving within a week of beginning the drug trial," said Wood.

"I have just returned from the huge Round The Island Yacht Race, which is a testament to my better health. I was diagnosed with prostate cancer after reading about the symptoms in the newspaper and immediately went to the GP. My life might have turned out very differently if I hadn't read that article," he added.

Another patient, Simon Bush, 50, a bank manager from London, was also enrolled on the trial.

"Last year I was in severe pain because of my prostate cancer, which had worsened and spread to my bones," said Bush.

"Chemotherapy and other treatments had failed and news that I had very few treatment options available to me was devastating for my family," he added, saying that abiraterone has allowed him to continue with his interests like fitness and travelling, and to "have a year so far of near normality".

Abiraterone is owned by BTG and licensed to Cougar Biotechnology, Inc of Los Angeles, California. Further trials of the drug are under way, including an international study on men with prostate cancer and a UK study on women with breast cancer.

Chief Executive of the Institute of Cancer Research Professor Peter Rigby, said the trial result showed what can be achieved by funding world leading cancer research:

"Today we can reveal a potential major advance in the treatment of prostate cancer. We hope with the generous contribution of the community we can continue to develop better treatments to combat many cancers."

These sentiments were echoed by Cally Palmer, Chief Executive of The Royal Marsden NHS Foundation Trust, who said:

"The results of this study show just how important abiraterone is set to become in the treatment of men with prostate cancer and highlights the national importance of funding pioneering cancer research."

"Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven.

Gerhardt Attard, Alison H.M. Reid, Timothy A. Yap, Florence Raynaud, Mitch Dowsett, Sarah Settatree, Mary Barrett, Christopher Parker, Vanessa Martins, Elizabeth Folkerd, Jeremy Clark, Colin S. Cooper, Stan B. Kaye, David Dearnaley, Gloria Lee, and Johann S. de Bono

Journal of Clinical Oncology, Published online July 21, 2008.

DOI: 10.1200/JCO.2007.15.9749

Click here for Abstract.

Source: Journal abstract, Institute of Cancer Research press statement.

Choosing the Right Prostate Cancer Treatment (Video Medical And Professional 2020).

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