Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials
The Lancet, 04/30/2012
Rothwell PM et al. - 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.Methods
- This 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.
- 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 [HR] 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.