Researchers showed that measuring the numbers of circulating tumour cells in the blood predicted which men were benefitting least from a prostate cancer drug after as little as 12 weeks of treatment.
They hope their work will allow doctors to switch patients to alternative treatments earlier than is currently possible, if these results are confirmed by further studies. The research could also hasten the development of cancer treatments by speeding up clinical trials, since doctors could tell much earlier whether a treatment is working.
The study was led in the UK by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and also involved several leading international institutions.
It was funded by a range of organisations including a Medical Research Council biomarkers grant, the companies Janssen Diagnostics, the Prostate Cancer Foundation in the US, and Prostate Cancer UK.
As tumours grow and progress, they shed cancer cells into the bloodstream, some of which can seed new secondary tumours elsewhere in the body. So the researchers wanted to see whether a high number of circulating tumours cells was an indication of a growing tumour that wasn't responding to treatment, and could predict a lower chance of survival.
The study, published in the Journal of Clinical Oncology today (Monday), involved the detailed analysis of blood samples from 711 men who took part in a major phase III trial of the prostate cancer drug abiraterone.
Researchers measured numbers of circulating tumour cells at four-week periods after the start of treatment with the drug, along with a range of other biomarker molecules in the blood including lactate dehydrogenase (LDH), high levels of which are a sign of general tissue damage.
The trial itself had used the standard trial end points of average overall survival and survival free of cancer progression to show abiraterone's effectiveness in late-stage prostate cancer. But the researchers were able to cross-reference those results with data on circulating tumour cells and LDH levels in each man taking part.
They found a correlation between those men who had responded least well to treatment with abiraterone, and higher levels of cancer cells and LDH in the bloodstream, measured 12 weeks after starting treatment. They showed that levels of circulating tumour cells varied independently of a range of other biomarkers.
To prove the effectiveness of a new drug, clinical trials normally need to be run until the cancer is progressing clinically for each patient - and often until many of the patients on the trial have died. But with this new blood test, it might be possible to use circulating tumour cells as an early indicator that a drug is or is not working, and as a predictor of survival.
Study leader Professor Johann de Bono, Professor of Experimental Cancer Therapeutics at The Institute of Cancer Research, London, and Honorary Consultant at The Royal Marsden NHS Foundation Trust, said:
"The past decade has seen unprecedented success in the development of new drugs for advanced, metastatic prostate cancer. One of the major challenges we face now is in optimising the use of these new treatments by making sure that the right men receive them, and only for as long as they are benefitting.
"Our study showed that circulating tumour cells act as an early warning test for men who are not responding to treatment - potentially allowing doctors to switch patients early to alternative options. We hope our results will not only lead to better use of the current range of treatments, but also speed up the discovery of new drugs by providing an important new tool to the researchers trialling them."
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:
"Using a blood test to assess whether a cancer drug is working would be much easier and more convenient than other methods of monitoring treatment, and might pick up signs that a tumour is not responding weeks or months earlier than is achievable now. It could give doctors a valuable early warning that treatment is not working, and an opportunity to switch the patient promptly to an alternative drug."
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The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust 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 Royal Marsden NHS Foundation Trust
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 50,000 NHS and private 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, with the ICR, is the only National Institute for Health Research Biomedical Research Centre for Cancer. First awarded the status in 2006, it was re-awarded in 2011. A total of £62 million is being provided over five years, to support pioneering research work, and is being shared out over eight different cancer themes.
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 £100 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.