SAN FRANCISCO – The safety and efficacy profile of aspirin for preventing esophageal and other cancers is likely to limit its use to people at highest risk, said Dr. Janusz A. Jankowski in a presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
"The commonest question I’m asked is, ‘Should I now be taking low-dose aspirin?’," he said. "And my answer to that at this moment in time is indefatigably, no, you should not, unless you have a secondary risk factor," such as Barrett metaplasia or colon polyps (or a secondary cardiovascular risk factor).
Collectively, evidence suggests that taking aspirin reduces cancer risk by about one quarter, according to Dr. Jankowski; however, aspirin has to be taken for at least a decade to see clinically meaningful benefit (Lancet 2011;377:31-41). "Chemoprevention is a very, very long term goal here," he commented. "This is not about taking it for a few years and hoping to get a benefit – it’s 10 to 20 years. And that means that the side effect profile ... must be exceptionally low."
The risk of bleeding with aspirin is well known. Rates of any upper gastrointestinal bleeding and serious GI bleeding on the medication are about 4% and 2% per year, respectively, and aspirin particularly increases the risk of spontaneous GI bleeding after age 50 years. However, adding proton pump inhibitor (PPI) therapy largely attenuates the excess risk.
But new data have also implicated aspirin in the development of macular degeneration (Ophthalmology 2012;119:112-8). "That’s another thing that you may have to consider ... Could aspirin be causing something else, as well as preventing something?" said Dr. Jankowski, a visiting professor of GI oncology at the University of Oxford (U.K.) and the Honorary Sir James Black Professor at Barts and the London School of Medicine and Dentistry.
The authors of a recent analysis concluded that healthy people do not experience any significant reduction in either cardiovascular or cancer deaths when they take aspirin (Arch. Intern. Med. 2012;172:209-16), which "has kind of dashed our hopes for primary prevention," he said.
In the secondary prevention realm, the randomized Aspect trial (a phase III, randomized, study of aspirin and esomeprazole chemoprevention in Barrett’s metaplasia) is comparing lower- vs. higher-dose PPI therapy using esomeprazole. Each dosage level of esomeprazole is given with or without aspirin in about 2,500 patients with Barrett’s esophagus, which is thought to carry a 3%-5% lifetime risk of esophageal cancer.
In this trial, results for cancer and other clinical outcomes are not expected until 2019. But early endoscopic findings suggest that the added aspirin helps promote the appearance of new squamous epithelial islands in areas previously showing Barrett metaplasia, a promising surrogate end point, according to Dr. Jankowski.
At the same time, he cautioned against overreliance on aspirin, saying, "As good as aspirin is, ... it’s still not good enough because in fact we still don’t know who’s going to get a response, and we still think that the best response rate is probably only 20% in the population."
BADCAT (the Barrett’s Dysplasia and Cancer Task Force), which exhaustively reviews evidence on the topic, has identified aspirin effectiveness and responsiveness as an area of high priority for research. And because genetics have a major role here, the Chopin study (chemoprevention of premalignant intestinal neoplasia) is assessing genomewide associations in the development and prevention of esophageal cancer, including identification of aspirin-response genes.
Summing up the evidence on the use of aspirin to prevent esophageal and other cancers, Dr. Jankowski predicted, "In the next 2 years, there may very well be a recommendation that if you have secondary risk factors for cancer, like Barrett’s ... that you may be given aspirin therapy in addition to your proton pump inhibitor."
Only people in a fairly narrow age range will have net benefit, based on currently available data. "Aspirin is a wonderful agent. Having said that, there is no evidence whatsoever that even if you’ve got secondary risks factors for cardiac disease or cancer, you should take your aspirin before 55 years of age," he explained. And starting aspirin after age 75 years is not justified given the current human lifespan and the need for prolonged use to achieve benefit.
"The window of taking aspirin is between 55 and 75," he concluded, adding "while I am an enthusiast of aspirin ... it is only part of the jigsaw, and we still need even to answer that part."
Dr. Jankowski disclosed that he is a consultant to and receives research funding and honoraria from AstraZeneca.