Can humble aspirin rein in cancer?

Familiar drugs, such as aspirin, which eases fever and pain, and statins, which lower cholesterol, have something in common.

They are among an increasing number of old drugs that doctors are reassessing to treat other conditions, including cancer.

Statins are being studied to prevent prostate cancer and aspirin, to stop the recurrence of colorectal cancer .

A benefit of repurposing older drugs is their lower cost, given that many patients cannot afford expensive new drugs.

At the National Cancer Centre, Singapore (NCCS), doctors are looking at aspirin, a 100-year-old drug. Preliminary observations suggest that aspirin can nearly halve the risk of colon cancer deaths.

"Aspirin is the grandmother of all drug repurposing," said Dr John Chia, a senior consultant medical oncologist at NCCS.

It was first used a century ago to treat pain and fever but, in the 1980s, doctors found that its mild "blood thinning" side effect was highly effective in preventing recurrent heart attacks and strokes.

Today, more than 100 million people take a baby aspirin pill each day to prevent blood clots.

Now, the interest in aspirin is no longer in relation to strokes and heart attacks but firmly on cancer.

"Drug repurposing can potentially see a cheap, good and powerful drug like aspirin prevent and even treat cancer effectively," said Dr Toh Han Chong, deputy director of NCCS. He and Dr Chia are leading the first global clinical trial, named Ascolt, to see if aspirin can stop the recurrence of cancer after surgery.

The multi-centre, randomised trial, which began in 2009, will study the role of aspirin in high-risk stage 2 and stage 3 colorectal cancer patients who have completed their standard cancer treatment.

Ascolt is cited often at international cancer meetings and in medical journals as one of the most important trials to watch, said Dr Chia.

In 2012, the National Cancer Institute in the United States listed aspirin's role in cancer treatment as one of the most provocative questions in cancer research.

The trial has recruited 800 of its target of 1,200 patients and is due to complete recruitment in two years.

The idea first came to Dr Toh and Dr Chia in 2006. They then wrote their first grant proposal for such a trial. From 2009, it took the doctors four years to build up a network of more than 60 partner hospitals in 11 other countries or special administrative regions in Asia.

These comprise China, India, Sri Lanka, South Korea, Taiwan, Malaysia, Indonesia, Hong Kong, Saudi Arabia, Australia and New Zealand.

If aspirin proves to be effective against recurrent cancer, it will change global clinical practice. Everyone with stage 2 or 3 colorectal cancer will be put on it, said Dr Chia. It will have an immediate impact and save 10,000 lives each year at a very low cost, he added.

Colorectal cancer is the most common cancer in Singapore, affecting about 1,000 people a year, and the third commonest in the world, affecting 1.2 million people.

Dr Toh noted that aspirin is important as there are now only a few drugs that can prevent high-risk stage 2 and stage 3 colon cancer from recurring after surgery.

"And there are many spectacular failures," he added. For example, there have been five clinical trials to test expensive therapies for stage 3 colon cancer but these were all negative. If the trials had been positive, the treatments would have added $50,000 to each patient's bill.

"In comparison, aspirin looks super cost-effective," said Dr Toh.

Despite the promise of an effective drug against recurrent cancer, it has been a struggle to find commercial funding for the trial.

This is mainly because aspirin is so cheap, costing 1 cent a tablet. It is not commercially viable for pharmaceutical firms to invest heavily in a large clinical trial. There will be little opportunity for them to recoup their investment, said Dr Chia.

Hence, he and Dr Toh have relied heavily on charities and foundations such Singhealth Foundation, Run for Hope, Lee Foundation, Lee Kim Tah and The Silent Foundation. Last month, they received more than $1 million from a private Swiss foundation called Rising Tide Foundation for Clinical Cancer Research.

"There is an urgent need for formal testing to change current clinical practice," said Ms Eveline Mumenthaler, director of the foundation.

The trial also secured early "seed funding" from the National Medical Research Council and support from the Singapore Clinical Research Institute.

Ascoltalso has Australian government funding to expand there.

Two years ago, the Australian Gastrointestinal Trial Group polled member doctors, patients and scientists. "Aspirin in colon cancer was polled as the No. 1 research priority," said Dr Eva Segelov from the University of Sydney, who is the co-chair for the study.

Patients and doctors are very enthusiastic about the trial. The group is now recruiting strongly in Australia and New Zealand, she added.

The trial doctors think there is a reasonable chance that the trial will show aspirin to be effective.

So do European experts, which is why there are two similar trialsbeing done by Dutch and British researchers this year, said Dr Toh. Two further trials are being planned in Sweden and Switzerland.

"Whenever a phase 3 drug trial is announced as positive, the share price of that pharmaceutical firm will go up," said Dr Chia. But in the case of aspirin, this "windfall" in benefits will accrue directly to patients and their communities, said Dr Toh.

This article was first published on December 8, 2015.
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