Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
Lancet. 2012 Apr 28;379(9826):1591-601. doi: 10.1016/S0140-6736(12)60209-8. Epub 2012 Mar 21.
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.
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.
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.
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.
None.
每日服用阿司匹林可降低某些腺癌的长期发病率，但由于某些癌症仅在几年后才出现死亡率的影响，这表明阿司匹林也可能会抑制肿瘤生长或转移。我们在每日阿司匹林（≥75mg/天）与对照组预防血管事件的 5 项大型随机试验中，确定了在试验期间发生癌症的患者中远处转移的发生频率。
我们的分析包括英国所有 5 项大型随机试验，研究每日阿司匹林（≥75mg/天）与对照组预防血管事件的效果。通过电子和纸质记录对所有新发癌症患者进行了回顾。根据肿瘤组织学（腺癌与其他）和临床特征，将阿司匹林对首发转移或后续随访（包括试验内癌症的试验后随访）风险的影响进行分层。
在平均 6.5 年（标准差 2.0 年）的试验随访中，17285 名试验参与者中有 987 人被诊断出患有新发实体癌。与对照组相比，阿司匹林组降低了远处转移的癌症风险（所有癌症，风险比[HR]0.64，95%置信区间[CI]0.48-0.84，p=0.001；腺癌，HR 0.54，95%CI 0.38-0.77，p=0.0007；其他实体癌，HR 0.82，95%CI 0.53-1.28，p=0.39），这主要是由于转移性腺癌的比例降低（比值比[OR]0.52，95%CI 0.35-0.75，p=0.0006）。阿司匹林降低了首发转移腺癌的风险（HR 0.69，95%CI 0.50-0.95，p=0.02）和首发无转移患者的后续随访中转移的风险（HR 0.45，95%CI 0.28-0.72，p=0.0009），特别是结直肠癌患者（HR 0.26，95%CI 0.11-0.57，p=0.0008）和直至诊断或诊断后仍继续接受试验治疗的患者（HR 0.31，95%CI 0.15-0.62，p=0.0009）。与对照组相比，阿司匹林降低了患有腺癌患者的癌症死亡风险，尤其是那些首发时无转移的患者（HR 0.50，95%CI 0.34-0.74，p=0.0006）。因此，阿司匹林降低了试验人群中致命腺癌的总体风险（HR 0.65，95%CI 0.53-0.82，p=0.0002），但对其他致命癌症的风险没有影响（HR 1.06，95%CI 0.84-1.32，p=0.64；差异，p=0.003）。这些影响与年龄和性别无关，但吸烟者的绝对获益最大。一种旨在抑制血小板但生物利用度低的低剂量、缓释阿司匹林与高剂量阿司匹林同样有效。
阿司匹林可以预防远处转移，这可能是临床试验中每日阿司匹林与对照组相比癌症死亡率降低的原因。这一发现表明，阿司匹林可能有助于治疗某些癌症，并为专门预防远处转移的药物干预提供了原理证明。
无。
