Dublin, Ireland-Regular use of aspirin in the year before a diagnosis of stage I-III prostate cancer is associated with a reduction in prostate cancer-specific mortality, say Irish researchers.
Aspirin inhibits cyclo-oxygenase-2 (COX-2), which is expressed in response to tumor promoters. Overexpression of COX-2 occurs in primary prostate tumors, and COX-2 has been shown to be associated with more advanced tumors and poorer outcomes.
“Recent studies have demonstrated a reduction in prostate cancer mortality with aspirin use, but these studies did not provide information on the dose and timing of aspirin use. Our hypothesis was that as an anti-inflammatory agent and an antiplatelet agent, aspirin possibly has an effect in tumor development and the spread of micrometastases in the vasculature,” reported first author Evelyn M. Flahavan, MPharm, at the American Society of Clinical Oncology annual meeting in Chicago.
Cases of stage I-III prostate cancer (2,936 men) diagnosed from 2001 to 2006 were identified from the National Cancer Registry Ireland linked to the General Medical Services prescription refill database from community pharmacies. Men who had a supply of aspirin available to them in the year prior to diagnosis were identified as users.
“In Ireland, because low-dose aspirin is indicated for cardioprevention, it’s only available on prescription,” said Flahavan, a PhD student at Trinity College Dublin in Dublin, Ireland, working with Thomas Ian Barron, PhD, and colleagues.
Some 1,131 patients were classified as users. Aspirin use was stratified by dose (low, ≤75 mg; high, >75 mg) and dosing intensity (proportion of days in that year with aspirin supply available).
Cox proportional hazards models adjusted for age, smoking status, year of incidence, comorbidity score, Gleason score, tumor size, pre-diagnostic statin use, and receipt of radiation were used to estimate hazard ratios for associations between aspirin use and all-cause and prostate cancer-specific mortality.
Patients were followed up to Dec. 13, 2010 (median follow-up, 5.5 years). Aspirin use prior to diagnosis was associated with a non-significant reduction in the risk of prostate cancer-specific mortality, with an HR of 0.90 (95% confidence interval: 0.68 to 1.20).
Link between intensity, risk not significant
Patients with higher dosing intensity, defined as taking aspirin on 86% to 100% of days in the year preceding their diagnosis, were associated with a non-significant reduced risk (HR: 0.75; 95% CI: 0.51-1.09) in prostate cancer-specific mortality compared with intermittent use, which is consistent with recent meta-analyses and observational studies that have examined daily use of aspirin, Flahavan said.
In dose-response analyses, aspirin use was associated with a significantly lower risk of prostate cancer-specific mortality in men receiving >75 mg of aspirin (HR: 0.59; 95% CI: 0.35-1.00) but not ≤75 mg aspirin (HR: 1.01; 95% CI: 0.75-1.37).
“Although patients who took higher doses of aspirin had a statistically significant reduced risk, there are possible confounders that make patients who take higher doses different from those who take lower doses. That’s why the result should be interpreted with some caution, but we do see that there’s some association with a reduced risk of mortality,” Flahavan said.UT
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