Aspirin in the 21st century

Opportunities for treating cancer with aspirin

Dr Ruth Langley - University College London, London, UK

Many of the studies on the use of aspirin in CRC have focussed on prevention, but you talked about its use as a possible treatment.

Particularly in the last couple of years people have begun to think about aspirin as a treatment for cancer. Some of that activity has resulted from the work of Peter Rothwell who looked at a large number of vascular studies where patients had been allocated to aspirin and what he saw not only did aspirin decrease the risk of developing a cancer but it also appeared that there were less cancer deaths. When he looked at that in more detail he saw that these effects were happening quite early, probably within 1-3 years, and so that was the beginning of thinking that maybe aspirin could actually treat cancers because within that timeframe the cancers were almost certainly already there.

In addition to that, a number of people have been looking in various epidemiological studies and in big cancer registries to see if people who were diagnosed with cancer and were also receiving aspirin, how they did in comparison to people who weren’t on aspirin. What we’ve seen quite consistently, particularly in colorectal cancer, is that if you were on aspirin after your cancer diagnosis you appear to do better.

What is the evidence to support the treatment of CRC with aspirin?

I think we have to look across a number of areas. If you look at in vitro data and animal model data, looking back, in fact, many, many years it appears that aspirin prevents the development of metastases and that may be how it’s working as a treatment. We’re now, as I’ve just said, putting that together with the data from clinical trials and from epidemiological studies and feeling that there’s certainly some evidence that aspirin could be effective and we need to work out how to use it within all our normal treatment paradigms.

Can you outline some of the oncology trials that are being performed with aspirin?

There are a number of trials. Probably the most activity is in the adjuvant setting. The first trial, really, was the ASCOLT study which is being run in a number of countries, including Singapore and Australia. There they were looking at using aspirin after a diagnosis of colorectal cancer. Here in the UK we’re just about to start a large study called the Add-Aspirin study and within that there are actually four separate trials, one in colorectal cancer, one in breast cancer, one in gastro-oesophageal cancer and one in prostate cancer. In each of those patients will be randomised after they’ve had their treatment to either a placebo, aspirin 100mg daily for at least five years or aspirin 300mg daily for at least five years. Then we’ll be looking to see whether aspirin can prevent or delay the cancers coming back and also looking at other aspects, for example, how do these patients do from a cardiovascular point of view.

Can you tell us more about the Add-Aspirin trial and its current status?

It’s just about to open. We’re hoping that the first patients will be recruited in October 2015. We’re planning to open in nearly a hundred centres across the UK. For the gastro-oesophageal and the breast cohorts the trial will also be run in India and we’re expecting recruitment to start in India in about January 2016.

Can you outline the treatments that will be used in the Add-Aspirin trial?

No, for all the participants they will have had whatever is the standard treatment for the cancer they’ve got. So it may be surgery but then in quite a number of cases they may have chemotherapy before or after. In some cases they may have had, instead of surgery, they may have had radical chemoradiation, for example. So the concept very much is you have your best possible standard treatment and then you look to see whether you can add aspirin to it, which is why it’s called the Add-Aspirin study.

So taking breast cancer as an example, when would aspirin be used after?

For some of the hormonal treatments, both in prostate cancer and in breast cancer, because they’re long-term treatments you can join the Add-Aspirin study when you’re taking tamoxifen, for example.

What is the potential for the use of aspirin in the treatment of cancer in general?

There’s certainly some interesting data. If you look in the epidemiological literature certainly taking aspirin after breast cancer, for example, there’s some very interesting data there. In terms of prostate cancer there’s a trial that’s going to recruit patients in the UK where they’re looking at the group of men who have been diagnosed with prostate cancer but in general it’s felt not to be a particularly aggressive form of prostate cancer and those men are usually just put on surveillance. In that group they’re looking to see whether going on to aspirin can change their outcomes and that’s called the PROVENT study.

From a practical perspective, how should oncologists use aspirin right now?

There’s still quite a lot of debate about the role for aspirin, particularly in the treatment of cancer. So in any setting where we’re unsure we would encourage physicians and oncologists to take part in on-going trials and also for potential participants to discuss this with their oncologists.

What opportunities do you see for aspirin in the prevention or treatment of cancer in the future?

One of the most exciting things, actually, about aspirin is we don’t understand fully how the anti-cancer effects work. We don’t know whether the effects on primary prevention are working through the same mechanisms as they are in potentially stopping metastases, for example. So one of the things that we can do with these trials is that we can collect samples, both blood samples and tissue samples, and then we can work with our colleagues in the laboratory to look at the various pathways. There’s quite a lot of interest and excitement around platelets and that they may be either protecting tumour cells or they may be sending signals which make it easier or harder for cells to become malignant.

Do you have a final take-home message for patients?

If you’re talking to your oncologist and there is an opportunity of taking part in a clinical trial, it’s well worth having that conversation.