Comments from Professor Peter Rothwell on aspirin and cancer

21 March 2012

The Lancet is publishing a series of papers tomorrow on aspirin and cancer from Professor Peter Rothwell of the Nuffield Department of Clinical Neurosciences at the University of Oxford and colleagues.

The Lancet has issued its own press release.

Professor Rothwell can be contacted on +44 (0)1865 231610 or peter.rothwell@ndcn.ox.ac.uk.

He has also offered answers to the following questions in case they are helpful:

What do we know now about the benefits of daily low dose aspirin to prevent cancer?
We showed previously (Lancet 2007; 2010; 2011) that daily aspirin substantially reduces the long-term risk of some cancers, particularly colorectal cancer and oesophageal cancer, but that these effects don’t appear until about 8-10 years after starting treatment. The delay is because aspirin is preventing the very early development of cancers and there is a long delay between this early stage and the eventual clinical presentation with a cancer.

What we have now shown is that aspirin also has short-term effects, which are manifest after only 2-3 years. In particular, we show that aspirin reduces the likelihood that cancers will spread to distant organs by about 40-50%. This is important because it is this process of spread of cancer, or “metastasis”, which most commonly kills people with cancer.

These findings add to the case for use of aspirin to prevent cancer, particularly if people are at increased risk. Perhaps more importantly, they also raise the distinct possibility that aspirin will be effective as an additional treatment for cancer – to prevent distant spread of the disease.

More generally, no drug has been shown before to prevent distant metastasis and so these findings should focus future research on this crucial aspect of treatment of patients with cancer that hasn’t already spread.

What is the balance of risks and benefits with stomach bleeds and what should advice now be?
We also report two findings about the risk of stomach bleeds on aspirin. First, the excess risk of stomach bleeds on aspirin falls with prolonged use – and so the risks of long-term treatment with aspirin, as might be envisaged to prevent cancer, may well be less than was previously thought. Second, we showed that the risk of fatal stomach bleeds on aspirin is not increased compared with placebo. In other words, aspirin increases the risk of non-fatal bleeds from which the vast majority of people make a full recovery. The conditions that aspirin helps to prevent, on the other hand, such as cancer, stroke and heart attacks, are much more likely to be disabling or fatal.

Previous analyses of the balance of risk and benefit have simply counted the crude numbers of bleeds and other outcomes and have not considered the time-course of these risks or the severity of the different types of events.

How does this compare to benefits in preventing heart disease?
The benefits of daily aspirin in reducing the long-term risk of developing new cancers and in reducing the spread of existing cancers that have not yet presented are larger in absolute terms than the benefits in preventing heart disease and stroke – particularly with prolonged use. As rates of stroke and heart attacks in middle age continue to fall in the general population, whereas the rates of many cancers are stable or rising, the cancer benefit is likely to increasingly dominate risk/benefit analyses.

What do we now know about how aspirin leads to reduction in cancer deaths?
Is it some types of cancer in some people?It appears that there are two different processes, which may have different mechanisms. First, aspirin reduces spread of existing cancers, which appears from our data and previous research to be due to effect on platelets in the blood stream. Second, aspirin reduces the long-term risk of some cancers, which could also be due to effects of platelets, which release growth factors that can stimulate cancers to develop, but more research is required to fully understand this mechanism.

In terms of preventing spread of cancer, the data suggest that the effect is largest in adenocarcinomas. These include cancers of the gut, particularly colorectal cancer, some cancers of the lung and most cancers of the breast and prostate. In terms of preventing the longer-term development of new cancers, the largest reductions are seen in risk of colorectal cancer and oesophageal cancer, with smaller effects on several other common cancers.

Do the findings on metastasis mean that aspirin may have benefits as an additional treatment when cancer is diagnosed?
It seems likely that aspirin will be of benefit when started after cancer is diagnosed – assuming that it has not already spread. In the trials that we studied, patients were taking aspirin prior to the diagnosis of cancer and so we cannot be absolutely certain that the benefit will be there if it is started later. However, there are two encouraging findings in our reports. First, patients who started taking aspirin only a few weeks or months before a cancer was diagnosed had the same reduction in metastasis as people who had been taking aspirin for much longer. Second, most of the reduction was seen in those patients who had continued to take the aspirin up until or after they had a cancer diagnosed, whereas there was little benefit in those patients who stopped months or years prior to diagnosis. However, we argue in our papers that new trials are still required to confirm the benefit – but that such trials should be done urgently.

What has allowed you to mine so much new info from these previous studies?
Two things. First, the paper records of trials, such as these aspirin trials, are archived for many years after the trials are competed and published. This means that if new questions arise later, as is often the case, the potential to look back at what happened is not lost. Second, we looked at the effect on metastasis in large trials done in the UK. We were able to do this because the UK has an efficient system of cancer registration and death certification, data from which is made available for suitable research projects. We were therefore able to look at the risk and outcome of cancers that were diagnosed many years after the trials had finished. Few other countries have such well developed registration systems.
 
For more information please contact the University of Oxford press office on +44 (0)1865 280530 or press.office@admin.ox.ac.uk

Notes for Editors:

  • Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school.

    From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

    A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.