A set of 3 articles published in March in The Lancet and The Lancet Oncology may lead to new recommendations for aspirin as a preventive or even therapeutic agent against cancer.

Studies include proof in humans that a daily dose may guard against distant metastasis

A set of 3 articles published in March in The Lancet and The Lancet Oncology may lead to new recommendations for aspirin as a preventive or even therapeutic agent against cancer. The studies by Peter M. Rothwell, MD, PhD (University of Oxford and Radcliffe Hospital, Oxford, UK) and colleagues build on the group's previous work, which showed that daily aspirin reduces the long-term risk of death due to cancer.

“We have known about the link between long-term aspirin use and reduced risk of cancer deaths,” notes Rothwell. “The new findings involve shorter-term benefits, which appear related to aspirin's ability to reduce the risk of distant metastasis.”

In the first in the series of new articles, investigators report their analysis of data from 51 randomized trials of daily aspirin versus no aspirin, and show that daily low-dose aspirin reduced the incidence of cancer by about 24% after just 3 years and reduced cancer deaths by 37% after 5 years.

A second paper showcases new data demonstrating that 6.5 years of daily low-dose aspirin reduced the risk of cancer with distant metastasis by 36%, the risk of adenocarcinoma by 46%, and the risk of other solid cancers by 18%. The authors claim that the data represent the first proof in humans that aspirin prevents distant metastasis.

In the third paper, the authors compare randomized trials of aspirin with observational studies, and report that observational studies showed that aspirin reduced the risk of colorectal cancer by 38% compared to the 42% reduction shown in randomized trials. Similar correlations were found for esophageal, gastric, biliary, and breast cancer.

Cancer was not an endpoint for the randomized trials, as patients were receiving aspirin for the prevention of vascular events.

“Until Rothwell's January 2011 study in The Lancet, the most compelling link between aspirin and a lowered risk of cancer was for colon cancer,” says Andrew Chan, MD, of Harvard Medical School (Boston). “The new studies add to this data and show a consistency across randomized and observational studies that further suggest that the benefits of aspirin extend to other tumor types.”

Rothwell and colleagues noticed aspirin users had a reduced risk of distant metastasis, but found no difference in regional spread—leading them to suspect the antiplatelet action of aspirin limits the spread of cancer cells to other parts of the body. A variety of research suggests that COX-2 inhibition and other proapoptotic effects of aspirin also may play anticancer roles. “One of the things we're learning about aspirin is just how many different mechanisms it potentially influences,” notes Chan.

Gastrointestinal bleeding remains a concern as investigators discuss whether daily aspirin should be recommended, and to whom. The NCT01038583 and NCT00501059 trials now under way are also looking at side effects.

“As we move forward, it's likely that biomarker research will be increasingly important in determining which patients will preferentially benefit from aspirin, either as a preventive or therapeutic agent,” notes Chan. The Nonvascular Outcomes on Aspirin (NOVA) collaboration is tracking results from new trials and from follow-ups for previous trials.

Additional epidemiologic, basic, and clinical work on aspirin and related agents is underway and Rothwell hopes the latest studies spur further initiatives. “One area of research urgently needed is more clinical trials following the effects of aspirin on patients recently diagnosed with cancer to see if it can prevent metastasis and be used in combination with other therapies,” he says.