Combining prostate cancer drugs could delay drug resistance, study finds

Combining prostate cancer drugs could delay drug resistance, study finds Tuesday 1 May 2012 Combing two new prostate cancer drugs could increase the number of men who respond to treatment and the length of time they benefit, research led by The Institute of Cancer Research (ICR) has shown. For many years, the only effective treatment for men with advanced prostate cancer who had become resistant to standard hormone therapies was the chemotherapy docetaxel. Recent trials led by the ICR and The Royal Marsden NHS Foundation Trust have since found that two new types of hormone-blocking drugs, abiraterone acetate and MDV3100, can extend life for men with advanced prostate cancer. Thanks to these trials, abiraterone, which was discovered at the ICR* in what is now the Cancer Research UK Cancer Therapeutics Unit, has now been licensed in the US and Europe, while the manufacturers of MDV3100 will apply for approval later this year. A new study published in Cancer Research has today identified a reason why men ultimately develop resistance to abiraterone. In a laboratory study, Dr Gerhardt Attard from the ICR and The Royal Marsden and colleagues found that steroids and other drugs given in combination with abiraterone to control side-effects could contribute to resistance by activating mutations in the hormone-receptor gene. Importantly, the team found that it was possible to block this activation by combining abiraterone with MDV3100. This is the first ever study to give a biological reason for combining these two new drugs. Lead author Dr Attard says: “Abiraterone is an effective treatment for the majority of men with advanced prostate cancer, but sadly they all eventually develop resistance. Our study suggests we should combine prostate cancer drugs rather than giving them sequentially. If the results hold true it patients, this could delay drug resistance and also increase the number of men who benefit. Clinical trials are now being planned to test the combination of abiraterone and MDV3100.” The scientists also found that at high doses, abiraterone could also block the androgen receptor like MDV3100 does. Study co-author Professor Johann de Bono from the ICR and The Royal Marsden says: “Abiraterone is normally given at 1000mg/day but it is safe at double this dose, and at this level it may have a similar ability to block resistance, so this is another promising avenue to explore. Around 10,000 men a year in the UK are diagnosed with advanced prostate cancer and so our findings have the potential to benefit thousands of men.” The study received funding from the Prostate Cancer Foundation and Prostate Action, along with Cancer Research UK and the Department of Health. -ENDS- Media Contact: ICR Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900 * Abiraterone was discovered at the ICR in research supported by grants from Cancer Research Campaign (now Cancer Research UK), the Medical Research Council (MRC) and BTG International LTD. Subsequent patient trials and further research on abiraterone was supported by Cougar Biotechnology Inc. / Janssen Pharmaceutical Companies, Cancer Research UK, Experimental Cancer Medicine Centre, the MRC, BTG International Ltd, Prostate Cancer Foundation, Prostate Cancer Research Foundation, Prostate Cancer Charity, the ICR and The Royal Marsden. Cancer Research Technology assigned abiraterone acetate to BTG International Ltd, who in turn licensed it to Cougar Biotechnology Inc., now a member of the Janssen Pharmaceutical Companies. “Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100” with corresponding author Gerhardt Attard publishes in the print edition of Cancer Research on Tuesday 1 May 2012. The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research institutes. Scientists and clinicians at the ICR are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally. The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment. As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public. The ICR’s mission is to make the discoveries that defeat cancer. For more information visit www.icr.ac.uk. The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education. Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex. Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital. For more information, visit www.royalmarsden.nhs.uk

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