Studies add to evidence that aspirin may help prevent, treat cancer

Issue: April 25, 2012

Results of three recently published studies add to the evidence that suggest daily aspirin can help prevent cancer and possibly aid in treatment.

Peter M. Rothwell, MD, PhD, FRCP, professor of clinical neurology at the University of Oxford and a clinical neurologist at John Radcliffe Hospital in Oxford, previously found that daily doses of aspirin — even as low as 75 mg per day — reduce long-term risk of developing certain cancers, although treatment may take up to 10 years to yield benefit. Rothwell and colleagues conducted the current studies to examine the short-term effects of daily aspirin.

In the first study, published in The Lancet, the researchers evaluated data from 51 randomized trials in which 77,549 participants were assigned to daily aspirin or no aspirin to determine the drug’s effects on myocardial infarction and other vascular events. They also measured all deaths, including those due to vascular death and cancer.

The researchers determined that the risk for cancer death was 15% lower in the aspirin group vs. the control group (OR=0.85; 95% CI, 0.76-0.96). Those who took daily aspirin for 5 years or longer had a 37% reduced risk for cancer death compared with controls (OR=0.63; 95% CI, 0.49-0.82).

Results of six of the trials (n=35,535) demonstrated that daily low-dose aspirin for 3 years or more reduced cancer incidence by 24% (OR=0.76; 95% CI, 0.66-0.88). Case-fatality from major extracranial bleeds was about 68% lower among those on daily aspirin compared with controls.

“Alongside the previously reported reduction by aspirin of the long-term risk of cancer death, the short-term reductions in cancer incidence and mortality — and the decrease in risk of major extracranial bleeds with extended use, and their low case-fatality — add to the case for daily aspirin in prevention of cancer,” Rothwell and colleagues wrote.

Second study

For the second study, also published in The Lancet, the researchers analyzed five randomized trials involving participants (n=17,285) assigned to at least 75 mg daily aspirin or no aspirin to determine its effect on prevention of vascular events. The researchers collected data on metastases of cancers that were diagnosed during the trial periods. Mean follow-up was 6.5 years.

Aspirin reduced the risk for cancer with distant metastasis by 36% (HR=0.64; 95% CI, 0.48-0.84) and reduced the risk for adenocarcinoma with metastasis by 46% (HR=0.54; 95% CI, 0.38-0.77).

Aspirin reduced the risk for adenocarcinoma with metastasis at initial diagnosis (HR=0.69; 95% CI, 0.50-0.95) and risk for metastasis on subsequent follow-up in patients who did not have metastasis initially (HR=0.45; 95% CI, 0.28-0.72), the researchers said. The risk was particularly lower among patients with colorectal cancer (HR=0.26; 95% CI, 0.11-0.57) and among patients who stayed on trial treatment up to or after diagnosis (HR=0.31; 95% CI, 0.15-0.62).

The study results showed aspirin reduced death due to cancer by 50% in patients who developed adenocarcinoma without metastasis at diagnosis (HR=0.50; 95% CI, 0.34-0.74). Overall risk for fatal adenocarcinoma was 35% less among those assigned to aspirin (HR=0.65; 95% CI, 0.53-0.82). Aspirin did not reduce the overall risk for other fatal cancers.

The effects were independent of gender and age, the researchers said.

“These findings provide the first proof in man that … aspirin also prevents distant cancer metastasis,” the researchers wrote. “That aspirin prevents metastasis at least partly accounts for the reduced cancer mortality … and suggests that aspirin will also be effective in treatment of some cancers.”

Third study

The third study — published in The Lancet Oncology — involved a systematic review of case-control and cohort studies published from 1950 to 2011 that reported associations between aspirin use and risk or outcome of cancer.

The case-control studies showed that regular aspirin use reduced risk for colorectal cancer by 38% (OR=0.62; 95% CI, 0.58-0.67). Those findings were similar to the effect of daily aspirin on 20-year risk for death demonstrated in the randomized trials (OR=0.58; 95% CI, 0.44-0.78). Researchers also identified similar risk comparisons for breast, biliary, gastric and esophageal cancers.

Regular aspirin use also was associated with a reduced risk for cancers with distant metastasis (OR=0.69; 95% CI, 0.57-0.83), the researchers said.

“Estimates from case-control studies and well-designed cohort studies of the effect of aspirin on long-term incidence and mortality due to cancer and of effects on metastasis are consistent with those from randomized trials,” the researchers wrote. “Follow-up of trials of daily aspirin vs. control has so far lacked the statistical power to establish effects of aspirin on incidence and outcome for several common cancers, particularly those occurring only in women, and there is an urgent need for more data for effects on metastasis when aspirin is started after diagnosis of cancer.”

In an accompanying editorial in The Lancet, Andrew T. Chan, MD, MPH, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, and Nancy R. Cook, ScD, of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said the three studies yielded “compelling” results, but they have limitations.

The analyses do not include data from large randomized trials such as the Women’s Health Study, in which 39,876 women were treated with 100 mg aspirin every other day for 10 years, or the Physicians’ Health Study, in which 22,071 men were treated with 325 mg aspirin every other day for 5 years. Those studies, which included follow-up of 10 to 12 years, demonstrated that aspirin was not associated with reduced risk for colorectal cancer, overall cancer incidence or overall cancer mortality, according to Chan and Cook.

Also, researchers did not obtain information about cancer screening or surveillance because the studies were designed to examine cardiovascular endpoints. The potential for earlier diagnosis or treatment due to bleeding or anemia associated with aspirin use could explain some of the results, Chan and Cook said.

“These caveats notwithstanding, Rothwell and colleagues show quite convincingly that aspirin seems to reduce cancer incidence and death across different subgroups and cancer sites, with an apparent delayed effect,” they wrote. “Rothwell and colleagues’ impressive collection of data moves us another step closer to broadening recommendations for aspirin use. Moreover, future evidence-based guidelines for aspirin prophylaxis can no longer consider the use of aspirin for the prevention of vascular disease in isolation from cancer prevention.”

Algra AM. Lancet Oncol. 2012;doi:10.1016/S1470-2045(12)70112-2.
Chan AT. Lancet. 2012;doi:10.1016/S0140-6736(11)61654-1.
Rothwell PM. Lancet. 2012;doi:10.1016/S0140-6736(12)60209-8.
Rothwell PM. Lancet. 2012;doi:10.1016/S0140-6736(11)61720-0.

Disclosure: The researchers report no relevant financial disclosures.