IARC 50th Anniversary Conference

MetAL trial for prostate cancer

Dr Mieke Van Hemelrijck - Kings College London, London, UK

There are a lot of epidemiological studies suggesting that metformin may be associated with a lower risk of getting prostate cancer and other studies then suggest that it may slow down progression of disease. However the evidence to date is still inconclusive because some studies then show the opposite.

Do we have any insights into potential mechanisms?

Similarly to epidemiological studies there are a lot of experimental studies going on thinking of different mechanisms such as fatty acid synthase but again some studies suggest that it’s a tumour inhibitor but then others suggest that it’s suppressing the tumour. So again there is inconclusive evidence from experimental studies.

Metformin is typically identified with diabetes, what prompted people to look at it with cancer?

People have been looking at comorbidities of patients who present with cancer and what happened is that people saw… there are some epidemiological studies, actually, suggesting that diabetes is protective for getting prostate cancer, it’s also protective for dying from prostate cancer. Then some people think that there are underlying biological mechanisms supporting that and others think that it may have to do with errors in the statistical analysis. So again there is a lot of confusion about what really is going on with metformin. But it would be great if something is going on because metformin is cheap, it’s safe, there is very minor adverse events following treatment with metformin so it would be really great if there is a subgroup of prostate cancer patients who would benefit from getting metformin.

Could you tell us about your study?

We’re running a window of opportunity trial which is called MetAL, which stands for Metformin and Longevity. The idea is really to try and understand what are the underlying biological mechanisms linking metformin and prostate cancer. Because before we can really do a trial to investigate how metformin can slow down prostate cancer we have to have some understanding of what it is potentially doing to the prostate tissue. So we’re taking tissue from men who are diagnosed with prostate cancer and then we randomise them to either get a placebo or metformin and then three or four weeks later they have their radical prostatectomy, so their surgery for prostate cancer. So that means that we have tissue before and after having been exposed to metformin, both from the metformin group and the placebo group. So the idea is to actually stain the tissue and look for different markers of different pathways to try and see what metformin really is doing with prostate tissue.

What message would you give to medical professionals and cancer doctors at this point?

At the moment it seems like something is going with diabetes and prostate cancer in itself because it’s not only diabetes being associated with the risk of getting prostate cancer or not being associated with it but it’s also some of the drugs for prostate cancer may cause an increased risk of getting diabetes. So at least we need a multidisciplinary team making sure that we look for potential indicators of risk factors for diabetes and that things get managed at the same time that cancer doctors talk to endocrinologists and the other way around to improve the care of our prostate cancer patients.

What is your take-home message?

I think there is a whole debate about repurposing drugs for cancer. There is definitely potential, given that these drugs are cheap and safe but I don’t think we should start getting excited as of yet. I think we first have to have a better understanding of what are the underlying biological mechanisms so that we can target the right patients.