Tuesday, 7 June 2011

Janusz Jankowski et al comment on Peter Rothwell, Asprin & Cancer, 14 May 2011, The Lancet

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Janusz Jankowski, Hugh Barr, John deCaestecker, Peter Watson, Stephen Attwood, Paul Moayyedi

We write with regard to the Article by Peter Rothwell and colleagues,1 which indicates that low-dose aspirin might prevent cancer. Although we strongly endorse Rothwell and colleagues’ publication, we urge caution.

If we presume that aspirin does have a chemoprotective role, it clearly does not work for everyone since at best 25% of people are estimated to get a cancer prevention benefit but this figure could be as low as 20%.

This “aspirin resistance” in patients seems to be present widely in the population so we do not know who should respond.2

Genetic studies such as those undertaken by the Esophageal Adenocarcinoma Genetic Linkage (EAGLE) consortia are needed to assess which individuals will respond best to the chemopreventive eff ects of low dose aspirin.

Additionally, meta-analysis of cardiac trials with reassess ment of causes of cancer deaths might have in advertently introduced bias. For example, the number of cases of gastrointestinal cancer death in Rothwell and colleagues’ study was 182 out of almost 20 000 cases. In particular there were only 23 oesophageal cancers. Patients in these trials, especially those using aspirin, might have had complications that resulted in earlier presentation.

The AspECT chemoprevention trial 3 was specifi cally designed to look at the effect of aspirin on oesophageal cancer development but will also give information on effects on colon cancer development as well as on cardiac deaths. To date, the data monitoring team and the trial steering team have not divulged any obvious trend between the four groups of this trial (low-dose proton-pump inhibitor [PPI], high-dose PPI, low-dose PPI with low-dose aspirin [300 mg], and high-dose PPI with low-dose aspirin). We need trials such as AspECT to report their preliminary findings of genetic stratification for response, as well as risk/benefi t, dose, and length of therapy.

JJ has a consultancy to AstraZeneca Oncology, which makes esomeprazole—one of the agents in the AspECT trial. JJ has also received grants in aid from AstraZeneca previously. All authors are co-investigators in the AspECT trial. *Janusz Jankowski, Hugh Barr, John deCaestecker, Peter Watson, Stephen Attwood, Paul Moayyedi Leicester Royal Infi rmary, Leicester LE7 7HH, UK (JJ, JdC); Gloucestershire Royal Hospital, Gloucester, UK (HB); Belfast Hospital Trust, Belfast, UK (PW); Northumbria Healthcare NHS Foundation Trust, Tyne and Wear, UK (SA); and Gastrointestinal Division, McMaster University Medical Centre, Hamilton, ON, Canada (PM)

1 Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Eff ect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31–41.
2 Jankowski J, Hunt R. Cyclooxygenase-2 inhibitors in colorectal cancer prevention: better the devil you know. Cancer Epidemiol Biomarkers Prevent 2008; 17: 1858–61.
3 Das D, Chilton AP, Jankowski JA. Chemoprevention of oesophageal cancer and the AspECT trial. Recent Results Cancer Res 2009; 181: 161–69.

Peter Rothwell Reply (full text)  - Risk of GI Bleeds
 Mark Nelson raises the issue of the risk of bleeding on aspirin. We deliberately made no specific recommendations about the widespread use of aspirin in healthy individuals, but we did discuss the issue of bleeding in some detail. Our analyses showed that taking aspirin daily for 5—10 years would reduce all-cause mortality (including any fatal bleeds) during that time by about 10% in relative terms. Subsequently, there would be further delayed reductions in risk of cancer death even if aspirin was stopped. In healthy middle-aged individuals, the risk of major bleeding on aspirin is relatively low (about 0·2 per 1000 patients per year—only a small proportion of which are fatal), and is already offset in many groups by the small reduction in risk of ischaemic vascular events. The reduction in risk of cancer is therefore additional to this existing balance in which the bleeding risk is already taken into account. However, the risk of bleeding on aspirin increases steeply with age and so we did not comment on use of aspirin in healthy individuals older than 75 years. The results of the ASPREE trial will be of great importance in this respect. 

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