Tuesday 7 August 2012
Patients in early clinical trials of new-style targeted cancer therapies appear to have a much lower risk of the most serious side-effects than with traditional chemotherapy, according to a new analysis.
Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust analysed data from 36 Phase I trials run by the organisations’ joint Drug Development Unit.
The study, published today in August’s Annals of Oncology, found the overall risk to patients of suffering a life-threatening side-effect was around seven times less than for traditional cytotoxic agents*.
Most new cancer drugs developed over recent years are targeted agents, which attack the specific genetic or molecular faults driving cancer growth, rather than one-size-fits-all chemotherapeutics, which kill all rapidly dividing cells.
Recent studies have shown that patient response rates in Phase I trials of new-generation targeted drugs are approximately two-fold higher than for old-style drugs. But until now, the risk of side-effects to patients taking part in early stage trials of new-style drugs has been unclear.
Senior author Dr Rhoda Molife, a medical oncologist and senior investigator in Phase I clinical trials in the Drug Development Unit of The Institute of Cancer Research and The Royal Marsden, said: “Our study found that the risk of developing a serious side-effect in a Phase I trial of a targeted drug was relatively low, compared with previous analyses of similar trials of old-style chemotherapies.
“The theory behind targeted drugs is that they should affect only cancer cells that have a specific fault and spare healthy cells, which we hoped would lead to higher rates of efficacy and lower rates of side-effects. It’s very pleasing that our study seems to back this up, at least in the context of Phase I trials.”
“Importantly, we also identified characteristics that put patients at higher risk of these toxicities, including if they were sicker when joining the trial. This will help doctors make the right choices about who should be given new drugs in early stage clinical trials.”
Scientists retrospectively analysed data from 687 patients treated at the Drug Development Unit of The Institute of Cancer Research and The Royal Marsden between January 2005 and December 2009. They had a range of cancer types, with gastrointestinal, gynaecological and sarcoma the most common.
The Drug Development Unit of The Institute of Cancer Research and The Royal Marsden is supported by the National Institute for Health Research Biomedical Research Centre for Cancer, and also receives funding from Cancer Research UK and the Experimental Cancer Medicine Centre network.
For targeted drugs, the most common toxicities were gastrointestinal – such as loss of appetite, diarrhoea and vomiting – and fatigue, while side-effects for cytotoxic drugs are generally haematological or cardiovascular in nature
Patients were more likely to suffer side-effects if they were given a higher dose than that which the trial later found to be optimal, or if they were sicker when they joined the trial. The findings should help guide researchers in selecting patients for trials and improving trial design.
Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: “The discovery of targeted therapies is revolutionising the way we treat cancer, and is a key focus of our research here at The Institute of Cancer Research. Many of these drugs have individually transformed the care of certain cancers, but the strength of this study is that it helps confirm the validity of the overall approach.”
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Notes to editors:
“Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience” with corresponding author L. R. Molife publishes in the August issue of the Annals of Oncology.
* The overall risk to patients of suffering a Grade 4, life-threatening, side-effect in this study was 1.9 per cent, compared with 14 per cent found in an analysis of trials from 1991 to 2002. The risk of a Grade 3, severe, side-effect in this study was 14.1 per cent, compared to 10-36 per cent found across two previous analyses of Phase I trials of cytotoxic agents.
Phase I trials are designed to evaluate the drug’s safety and also the optimal dose to give to patients. As these small trials represent the first time a drug has been tested in people, its effectiveness and side-effects are not yet known and so patients who are considering taking part face many uncertainties.
Although the specific side-effects of each drug will differ, understanding average responses is important so doctors can help patients evaluate whether to participate. Some side-effects are unavoidable as doctors try to establish the most appropriate dose for patients.
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. The Cancer Therapeutics Unit and Drug Development Unit at the ICR and The Royal Marsden were recently honoured with the 2012 American Association for Cancer Research Team Science Award for the “tremendous impact” of their preclinical and clinical studies.
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 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 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
The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (www.nihr.ac.uk).
This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily
those of the NHS, the NIHR or the Department of Health.
The Experimental Cancer Medicine Centre Network
The Experimental Cancer Medicine Centre (ECMC) network is jointly supported by Cancer Research UK, the National Institute for Health Research in England, and the Departments of Health of Scotland, Wales and Northern Ireland. It launched in 2006, with £35M funding over five years, with a further £35M announced in 2011 for five more years to fund centres across the UK. Each ECMC brings together lab-based experts in cancer biology with cancer doctors to speed up the flow of ideas from the lab bench to the patient’s bedside. Find out more at www.ecmcnetwork.org.uk
Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research
- The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1861 or visit www.cancerresearchuk.org. Follow us on Twitter and Facebook