Aspirin Foundation Meeting 2013

Prevention of colorectal and lung cancer subtypes with aspirin

Dr Andrea De Censi - E.O. Ospedali Galliera, Genova, Italy

We don’t have data yet but we have a couple of ideas which we think are very good based on the work that Peter Rothwell has provided in the last few years showing that aspirin not only prevents colorectal cancer, which was a little expectable, but also has an effect on lung adenocarcinoma, which is the most important subtype. So this data provides the rationale for new studies to address specifically whether aspirin can prevent lung cancer.

We have selected the population at high risk for lung cancer who are the smokers, current or former, and who undergo the screening computerised tomography which has recently been shown in the big national US lung cancer screening trial to reduce by 20% the mortality from lung cancer. So we think that an ethical and rational approach for the reduction of mortality in this population is not only to screen and to try to check the disease in an earlier phase but also possibly intervene to revert the carcinogenesis progression. So we nested in these screening programmes the use of aspirin at low dose, using different endpoints as biomarkers of response because the large phase III trials probably need a lot of money and we should probably provide additional information proving the principle that aspirin can modulate the carcinogenesis progression.

So in the first study we are using the ground-glass opacities which are non-solid nodules which are quite frequent in the screening results in approximately 10-15% of the populations and there is data that these GGOs can represent the precursor lesion of lung cancer such as a typical adenomatous hyperplasia or a bronchial or alveolar carcinoma. The first study, led by Giulia Veronesi at the European Institute of Oncology, tried to assess whether aspirin given at the low dose of 100mg/day for one year can shrink the volume of these GGOs.

The second study has another principle, to try to see whether aspirin modulates the signature of microRNA in the blood. MicroRNAs are small fragments of RNA, non-coding arrangements of RNA which, however, are very important in regulating gene expression all over the body. There is a lot of data now that this mRNA can predict the risk of cancer, lung cancer and specifically aggressive lung cancer. So we are trying to both validate the biomarker, be it GGO or mRNA, as well as try to see whether the aspirin can affect these biomarkers. If these studies prove to be positive then we have a strong rationale for launching a larger, more expensive cancer mortality reduction trial.

The studies are about to be launched, the question, of course, is all about money – how to get the money to get the aspirin and placebo and take in the people who can help you to organise the recruitment. But our prior experience with inhaled budesonide, which is a corticosteroid, show that this population is very much keen to participate in trials, has a very high compliance. So we are optimistic about the initiation of these trials in the next few months.

Is the risk that patients will take aspirin and continue to smoke?

That’s a very good question. In fact, in the study of mRNA, which will be conducted in collaboration with Ugo Pastorino at the Istituto Tumori, it’s mandatory that the patients quit smoking or undergo a smoking cessation programme because one critic which I think has some fundament is that if you give a drug then the subject has an alibi to continue smoking. But it’s a debatable, very hotly debated, issue.