Expert opinion: aspirin and cancer – the unanswered questions

In the light of today’s headlines about aspirin and cancer, we spoke to one of our leading scientists Professor Janusz Jankowski, who’s running a clinical trial – AspECT – looking at whether aspirin can prevent oesophageal and bowel cancer. Here are his opinions and concerns about the latest findings:

Professor Janusz Jankowski

Aspirin’s ability to prevent cancer, especially cancers of the digestive system (oesophagus, stomach and bowel cancers) is well known.

But before we can recommend that people take aspirin, there are several important things to learn about whether long-term low-dose aspirin use is beneficial overall.

How common are side-effects?

Aspirin has several serious side effects. Most importantly, aspirin can increase the chances of developing stomach ulcers – which can cause bleeding. In people over 75, this can be fatal. The true frequency of aspirin-related stomach ulcers varies depending on the method used to measure it – it can be anywhere from 0.1 to 2 per cent of people taking aspirin, every year. However, drugs called ‘proton pump inhibitors’ can reduce the likelihood of bleeding from stomach ulcers caused by aspirin by up to fifty per cent.

Aspirin has other side-effects. In very rare cases, it can increase the chances of bleeding in the brain. About one in a hundred people taking aspirin have an allergic reaction. And about one in ten find it can make their asthma worse.

Who will benefit?

Secondly, because we’re all genetically different, and have different lifestyles, aspirin probably doesn’t prevent cancer in everyone who takes it. A reasonable estimate, based on the available research, is that about a quarter (25 per cent) of people will benefit – but this figure may be as low as a fifth (20 per cent). So the majority of people taking aspirin may not in fact benefit from it.

This ‘aspirin resistance’ seems to be widespread, and we don’t yet know what causes it.  So we don’t know who should take aspirin. To clarify this, we need large genetic studies to discover who will benefit from low-dose aspirin.

What dose?

Thirdly, we don’t know what dose of aspirin is best. While the current paper has looked at 75mg of aspirin we don’t know that 150 or even 300mg isn’t better. This is vital – the commonest reason drugs don’t work is the dose is wrong.

A premature rush to using aspirin in too small a dose in the population could result in many people being deprived of benefit.

How long should you take it for?

Fourth, we don’t know how long a person has to take aspirin to get a protective effect.

The current paper indicates an unusually rapid response for this: five years. This is unique and in many ways doesn’t fit with how we understand cancer develops.

In particular, in order to stop cancer developing we believe aspirin must be taken at a very early stage in cancer’s development, before it becomes ‘full-blown’ cancer. This prevents the small groups of abnormal cells obtaining more genetic changes that will eventually become cancer. We believe this takes about 10 to 15 years.

What has been done by Cancer Research UK in this area?

The trial I work on – AspECT – was specifically designed to measure rates of oesophageal cancer, bowel cancer and deaths from heart disease.

The trial is split into four groups:

• people only given a low-dose proton pump inhibitor
• people only given a high-dose proton pump inhibitor
• people given a low-dose proton pump inhibitor with 300mg aspirin
• people given a high-dose proton pump inhibitor with 300mg aspirin

To date, the team behind the trial haven’t revealed any obvious differences between these four groups. .

While we strongly endorse this recent study, much caution is needed. The study looked at trials that focused on heart disease rather than cancer, and that might have biased the results.

For example, the number of deaths from cancer of the digestive system was just 182 out of almost 20,000 patients. There were only 23 deaths from oesophageal cancer. That’s a very small number to be trying to draw firm conclusions from.

Patients on these trials, especially those who were taking aspirin, might also have had medical complications that resulted in them being diagnosed at an earlier stage (when cancers are easier to treat successfully).

In short, before making any broad recommendations, we need trials like AspECT to report their findings. AspECT’s preliminary data will be available in 2012. These will cover issues of risk benefit, genetic stratification for response, dose and length of therapy, and should go a long way towards answering these crucial questions.

Janusz Jankowski

Reference:

Rothwell, P., Fowkes, F., Belch, J., Ogawa, H., Warlow, C., & Meade, T. (2010). Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials The Lancet DOI: 10.1016/S0140-6736(10)62110-1