Aspirin & Cancer - the miracle willow that never quits

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Effect of Daily Aspirin on Risk of Cancer Metastasis: A Study of Incident Cancers During Randomised Controlled TrialsLancet. 2012 Mar 21;[Epub Ahead of Print], PM Rothwell, M , JF Price, JFF Belch, T Meade, Z MehtaTAKE-HOME MESSAGEAnalysis of results from five large clinical trials suggest that, in addition to reducing the long-term risk of adenocarcinoma, aspirin also decreases the risk of distant metastasis. Antiplatelet activity appears to play an important role in prevention of metastasis.EXPERT COMMENTARYLee S. Schwartzberg, MD, FACPDaily aspirin use reduces vascular events and is recommended for some groups of individuals as a prevention strategy. Previous study has suggested a role for aspirin in reducing cancer risks as well. A group of articles published simultaneously in The Lancet and The Lancet Oncology by Rothwell and colleagues at Oxford extend and refine the relationship between aspirin and cancer prevention. Analysis of all available randomized controlled trials showed that, after 3 or more years of therapy, aspirin reduced the absolute risk of cancer by 24% and the risk of 5-year cancer deaths by 37%. A further analysis revealed a fascinating corollary: aspirin reduced the risk of cancer metastases, particularly metastases from adenocarcinomas. Survival was better for individuals who took either high-dose or low-dose daily aspirin. A third study showed similar effects in observational trials, mirroring the randomized results. Taken together, the results of these trials strengthen the risk–benefit ratio toward using aspirin for prevention to reduce incidence of and death from cancer as well as vascular disease.AbstractBackground: Daily aspirin reduces the long-term incidence of some adenocarcinomas, but effects on mortality due to some cancers appear after only a few years, suggesting that it might also reduce growth or metastasis. We established the frequency of distant metastasis in patients who developed cancer during trials of daily aspirin versus control.Methods: Our analysis included all five large randomised trials of daily aspirin (≥75 mg daily) versus control for the prevention of vascular events in the UK. Electronic and paper records were reviewed for all patients with incident cancer. The effect of aspirin on risk of metastases at presentation or on subsequent follow-up (including post-trial follow-up of in-trial cancers) was stratified by tumour histology (adenocarcinoma vs other) and clinical characteristics.Findings: Of 17,285 trial participants, 987 had a new solid cancer diagnosed during mean in-trial follow-up of 6.5 years (SD 2.0). Allocation to aspirin reduced risk of cancer with distant metastasis (all cancers, hazard ratio

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0.64, 95% CI 0.48–0.84, p=0.001; adenocarcinoma, HR 0.54, 95% CI 0.38–0.77, p=0.0007; other solid cancers, HR 0.82, 95% CI 0.53–1.28, p=0.39), due mainly to a reduction in proportion of adenocarcinomas that had metastatic versus local disease (odds ratio 0.52, 95% CI 0.35–0.75, p=0.0006). Aspirin reduced risk of adenocarcinoma with metastasis at initial diagnosis (HR 0.69, 95% CI 0.50–0.95, p=0.02) and risk of metastasis on subsequent follow-up in patients without metastasis initially (HR 0.45, 95% CI 0.28–0.72, p=0.0009), particularly in patients with colorectal cancer (HR 0.26, 95% CI 0.11–0.57, p=0.0008) and in patients who remained on trial treatment up to or after diagnosis (HR 0.31, 95% CI 0.15–0.62, p=0.0009). Allocation to aspirin reduced death due to cancer in patients who developed adenocarcinoma, particularly in those without metastasis at diagnosis (HR 0.50, 95% CI 0.34–0.74, p=0.0006). Consequently, aspirin reduced the overall risk of fatal adenocarcinoma in the trial populations (HR 0.65, 95% CI 0.53–0.82, p=0.0002), but not the risk of other fatal cancers (HR 1.06, 95% CI 0.84–1.32, p=0.64; difference, p=0.003). Effects were independent of age and sex, but absolute benefit was greatest in smokers. A low-dose, slow-release formulation of aspirin designed to inhibit platelets but to have little systemic bioavailability was as effective as higher doses.Interpretation: That aspirin prevents distant metastasis could account for the early reduction in cancer deaths in trials of daily aspirin versus control. This finding suggests that aspirin might help in treatment of some cancers and provides proof of principle for pharmacological intervention specifically to prevent distant metastasis.