New hope on cancer survival

It’s hailed for helping prevent heart attacks — and now potentially even cancer. But worrying reports also link it to fatal falls and a higher risk of internal bleeding. So...

SCIENTISTS believe they could double the survival rates of people with advanced cancer within just ten years.

World-leading experts from the Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust in London said cutting-edge research will mean more patients get cured while others live far longer.

This could include using genetically modified viruses to target cancer cells and combining existing treatments.

Around 167,000 people die from the disease every year in the UK. Dr Olivia Rossanese of the ICR said they hope to ‘overcome cancer’s deadly ability to evolve and resist treatment’.

FORTy years ago a bountifully cheap painkiller was hailed as a wonder drug for preventing heart disease by making blood less sticky and thus less liable to form artery-clogging clots. Doctors began to recommend that anyone over the age of 55 who worried they were at risk of a heart attack could opt to take the drug daily.

Then, eight years ago, this same medicine was proclaimed to be one of our best weapons against cancer, thanks to its ability to reduce levels of cell-damaging inflammation in our bodies. Again, some doctors began to recommend taking a daily preventive dose.

That drug is aspirin, which is now taken once a day in low doses of 75mg to 100mg by millions as a preventive therapy for circulatory diseases and cancers, and by countless others in high doses (300mg and above) for pain, headache and fever.

This humble ‘wonder pill’ costs less than a penny to make — some 40,000 tonnes of the medicine (almost four times the weight of the Eiffel Tower) are produced globally each year. But aspirin’s glittering star is now in danger of fading.

New research is increasingly reinforcing warnings that the drug’s side-effects, which include internal bleeding and gastric ulcers, are so prevalent that the risks of taking even daily low-dose aspirin can, for many people, seriously outweigh any benefits in preventing serious illness.

Nevertheless, some doctors maintain that significant numbers of patients should still benefit from a daily dose.

Indeed, one leading UK-based researcher passionately maintains that aspirin has not been trialled fairly and we are all missing out on its potential life-saving benefits.

The mixed messages have left many in a dilemma, wondering whether they should ditch the daily pill that doctors had been urging them to take until recently.

Salicylic acid, the natural substance that is the key ingredient in aspirin, is found in willow tree bark. It is cited in 4,000-year- old scripts as a painkilling salve for rheumatism. Hippocrates, the Ancient Greek father of medicine, recommended it for fever, pain and childbirth.

Meadowsweet, another plant source of salicylic acid, was a sacred herb to British Druids and is mentioned by Chaucer in the 14th century.

In the 1700s, an English clergyman, the Reverend Edward Stone, performed the first scientific study of willow bark and wrote to the Royal Society saying he had used it successfully to treat fever in 50 of his parishioners.

But it was a German chemist, Dr Felix Hoffmann, who invented a lab-made version of the meadowsweet ingredient, acetylsalicylic acid, in 1897 as a painkilling drug. This spawned today’s pharmaceutical industry.

The compound was registered as Aspirin (the ‘A’ comes from acetyl and the ‘spir’ from meadowsweet’s scientific name at the time, Spiraea ulmaria).

CAN A LOW DOSE PREVENT CANCER?

AFTER World War II, doctors around the world began to notice that patients regularly taking aspirin for chronic pain had lower rates of heart disease.

And in 1980, Professor Richard Peto, an epidemiologist at Oxford University, published an analysis of six studies and concluded that people on aspirin lowered their risk of dying from vascular disease by nearly a quarter.

More recently, aspirin acquired renown for another preventive power. Around a decade ago, researchers began to conclude that aspirin’s anti-inflammatory properties meant that in low doses it could also prevent chronic damage to cells that can cause them to turn rogue and become cancerous.

In 2014, Jack Cuzick, a professor of epidemiology at Queen Mary University of London, wrote a review suggesting that more than 130,000 deaths from cancer would be avoided in the UK if everyone aged 50 to 64 took a low- dose aspirin daily.

The effects were greatest for bowel, stomach and oesophageal cancers, he said, with smaller effects for prostate, breast and lung cancers.

‘The second most important thing you can do to prevent cancer, after not smoking, is to take a lowdose aspirin,’ Professor Cuzick told journalists in 2015.

Since then, however, aspirin’s wonder- drug status has fallen into doubt.

For example, in 2016 a consortium of British, Spanish and U. S. researchers analysed results from 39 studies and warned that the risks of bleeding from low- dose aspirin regimens may outweigh their benefits in preventing cardiovascular disease, reported the journal PLOS One.

Since then, fears have steadily accumulated, to the point where in April, a key expert panel — the U. S. Preventive Services Task Force (USPSTF) — declared that people over 60 should not use daily aspirin to prevent a first heart attack because the benefit is outweighed by the potential risk of internal bleeding.

RISK OF BLEEDING MORE EASILY

THIS is a reversal of the guidance written by the same panel in 2009, which encouraged doctors to prescribe low- dose aspirin for preventing a first heart attack in men aged 45 to 79, and for the prevention of stroke in women aged 55 to 79.

Now the USPSTF says that the risks of internal bleeding from aspirin are higher than previously thought, and that those aged 40 to 59 must only take the medication daily if they are at a genetic risk of heart disease and after consulting a doctor.

Those over 75 should not take the drugs because there is little benefit in older age, it adds.

The NHS says you should only take daily low-dose aspirin if your doctor recommends it because of a high risk of heart attack or stroke, and warns that because aspirin helps to stop blood from clotting, taking it daily can make us bleed more easily.

It even cautions those taking it to be ‘careful when doing activities that might cause an injury or a cut. Use an electric razor instead of wet shaving, and use a soft toothbrush and waxed dental floss to clean your teeth.’

The NHS also warns that, as well

as causing intestinal bleeding, taking aspirin regularly can cause ulcers in the gut by damaging the stomach and intestinal lining.

The latest study to raise concerns about aspirin taken preventatively was published this month.

Australian researchers monitored more than 16,700 people aged over 70 for more than fourand-a-half years and found that those who took a daily low-dose aspirin had significantly raised risks of serious injury or fatality after a fall compared with older people who didn’t.

The study, published in the journal JAMA Internal Medicine, revealed that the drug made older people nearly 10 per cent more likely to have a fall that required hospital care.

This may be related to the drug’s anticoagulant effect: people who fall while taking aspirin may have considerable bleeding or bruising, prompting emergency care.

So is that it for preventive aspirin? Experts say that the picture is complicated.

Professor Colin Baigent, a director of the Medical Research Council ( MRC) Population Health Research Unit at Oxford University has been studying data on preventive aspirin since 1994.

‘Giving it to apparently healthy people is a very controversial matter,’ he told Good Health.

He explains that modern UK and EU guidelines recommend not giving daily aspirin to people who have not previously suffered a heart attack or stroke. ‘But for people who have already got a history of cardiovascular disease then aspirin is recommended for longer-term prevention of recurrent heart attack or stroke, because they are at high risk.’

However, he adds that the evidence suggests daily aspirin seems only to reduce the less severe (i.e. non-fatal) types of heart attacks.

‘It is not clear if aspirin does reduce the risk of a fatal heart attack, or reduce the risk of death or any death,’ he says.

‘That limited benefit must be balanced against the increased risk of gastrointestinal bleeding and also internal bleeding in the brain that is often fatal,’ adds Professor Baigent.

‘This is the dilemma people face. There is a tiny benefit of one in 1,000 people a year avoiding a heart attack. But there is a similar-sized increased risk of having a bleed.’

STATINS ‘SO MUCH SAFER’?

ONE possible answer is to target people better, by recommending daily aspirin only to people with higher risks of cardiovascular disease and stroke, such as smokers, people with a family history of circulatory disease, and those who are overweight.

‘Data gathered here at Oxford show the benefits are somewhat bigger — maybe two in 1,000, or more,’ says Professor Baigent.

‘But the things that put you at higher risk of a heart attack also put you at greater risk of having a bleed. So it boils down to a personal choice — say if you’re bothered about heart attack but not bleeding.

‘I think people should take daily low-dose aspirin (as is sold at pharmacy counters) only under a doctor’s guidance.

‘If you ask a doctor they are likely to say it’s up to you.’

In fact, Professor Baigent would recommend that people take statins where appropriate rather than aspirin, ‘ because they are so much safer’.

When it comes to cancer and other conditions, the picture is similarly complicated.

Jane Armitage, a professor of clinical trials and epidemiology at the Oxford MRC Population Health Research Unit, has run another tightly focused trial on daily aspirin.

This involved 15,500 otherwise healthy people with type 2 diabetes, a condition that significantly raises the risk of a heart attack or circulatory problems.

‘We found that daily aspirin brought a small reduction in heart problems — about 12 per cent — and also a commensurate increase in bleeding,’ Professor Armitage told Good Health.

‘As these people get older their risk of circulatory disease goes up, but so too does their risk of bleeding. It is very hard to get a sweet spot where you get more benefit than harm.’

Meanwhile, she says, there is also conflicting study evidence on the ability of a daily dose of aspirin to prevent cancer. ‘Older trials of aspirin show a reduction in risk of bowel cancer or deaths from bowel cancer. But at the end of our seven-year trial in 2018 we did not see any benefit.’

Professor Armitage adds: ‘There is uncertainty about other types of cancer and uncertainty about how quickly any beneficial effect might come in.

‘Data from older trials shows it may take up to 20 years for the benefit to appear. If you are taking aspirin for 20 years then you would expect there to be a lot of risk of bleeding as well.’

Such concerns do not dampen the long- standing enthusiasm for aspirin therapy displayed by Professor Cuzick — especially when it comes to one particular form of colon cancer, Lynch syndrome, or hereditary nonpolyposis colorectal cancer, which is caused by an inherited genetic defect. ‘ I think the evidence is overwhelming to show that preventive aspirin is highly beneficial,’ Professor Cuzick says.

And British researchers are currently examining whether regular aspirin use after treatment for an early- stage cancer can prevent a patient’s cancer returning.

The five-year Add-Aspirin trial is recruiting 11,000 participants with cancers of the breast, colon, stomach and prostate, in the UK, Republic of Ireland and India.

It is jointly funded by Cancer Research UK, the national Institute for Health and Care Research and the MRC’s clinical trials unit, and involves some of the UK’s leading hospitals, including specialist cancer hospital the Royal Marsden in London.

But Professor Cuzick argues that the drug should be used as a preventive therapy before people get cancer.

‘I believe that for the general population daily aspirin’s general cancer- prevention benefits hugely outweigh the risks,’ he says. ‘There is no doubt that bleeding is a real issue, but even with that the reduction in cancer risk outweighs it.’

The reason that conventional research doesn’t show a cancerprevention benefit, he argues, is that ‘you have to wait more than five years’ follow-up before you even start to find benefit.

‘If you do less then you just don’t see it. nothing happens in the first three years, only after five.’ Conventional research timespans tend to be too short to accommodate this, he says.

NEW STUDY WITH CANCER PATIENTS

PROFESSOR Cuzick is conducting the Aspirin for Cancer Prevention (ASCAP) trial, a long-running study of 2,000 otherwise healthy people taking daily aspirin, to establish if the volunteers’ incidence of any type of cancer is lowered, and to see what minimum dose of aspirin is needed for effect — in order to reduce the risk of bleeding.

‘We also need to find out who is at gastrointestinal risk,’ he says. ‘If we can find that out, then the rest of the population — most people — will benefit.’

The study began in 2018. ‘ We are a couple of years away from publishing the results — it’s really important to get this right because it’s been messed around with people overhyping negative results,’ he says.

As for his own health, Professor Cuzick says he has been taking low- dose aspirin daily for the past four or five years. ‘If you want to reduce your cancer risk, I recommend you keep your weight down, don’t smoke and take aspirin,’ he says.

‘I am 74, but would not generally recommend others to be taking it beyond the age of 70 because the bleeding risks rise as you get older. Our research findings suggest that you should take it between the ages of 50 and 65.’

But perhaps a bigger question is whether people would take aspirin every day for decades, going for years without seeing any tangible health benefit?

Professor Baigent has his doubts. ‘ Even in randomised, controlled trials of daily aspirin, where there’s quite a level of control over what people do, and compliance levels tend to be higher than in real life, after five years about half the people stop taking it,’ he says.

More importantly, however, the current consensus among UK, U. S. and EU regulators and medical authorities is that you should not self-medicate with aspirin, but discuss it first with your doctor.