MRC Clinical Trials Unit, University College London, UK.
The Christie Hospital, Manchester, UK.
Lancet Gastroenterol Hepatol. 2019 Nov;4(11):854-862. doi: 10.1016/S2468-1253(19)30289-4. Epub 2019 Aug 30.
Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer.
The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment.
After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants).
Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes.
Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.
临床前、流行病学和随机数据表明，阿司匹林可能预防肿瘤的发生和转移，从而降低癌症死亡率，特别是对胃食管和结直肠癌。正在进行评估原发性根治术后阿司匹林使用的随机试验。我们报告了 Add-Aspirin 试验的入组阶段的预先计划的可行性分析，以解决毒性问题，特别是胃食管癌根治治疗后的出血问题。
Add-Aspirin 方案包括四项 3 期随机对照试验，评估在四个肿瘤队列（胃食管、结直肠、乳腺和前列腺癌）中，每日服用阿司匹林对根治性癌症治疗后的复发和生存的影响。一个开放标签的入组阶段（阿司匹林 100mg 每日 8 周）在双盲随机分组之前进行（对于年龄小于 75 岁的参与者，阿司匹林 300mg、阿司匹林 100mg 或匹配的安慰剂以 1:1:1 的比例；对于年龄 75 岁或以上的患者，阿司匹林 100mg 或匹配的安慰剂以 2:1 的比例）。进行了预先计划的可行性分析，包括招募率、依从性和毒性。该试验在国际标准随机对照试验号注册中心（ISRCTN74358648）注册，并继续招募。
在招募 2 年（2015 年 10 月至 2017 年 10 月）后，登记了 3494 名参与者（胃食管癌队列 115 名，结直肠癌队列 950 名，乳腺癌队列 1675 名，前列腺癌队列 754 名）；2719 名（85%）完成入组期的 3194 名参与者继续进行随机分组，各肿瘤队列的入组率一致。2253 名患者的入组结束数据可用；2148 名（95%）参与者每周服用六到七片。11 名（0.5%）参与者在入组期间报告了 3 级毒性，胃食管癌队列无任何级别上消化道出血。总体最常见的 1-2 级毒性是消化不良（2253 名参与者中有 246 名，占 11%）。
阿司匹林在根治性癌症治疗后耐受性良好。毒性低，且在不同癌症队列之间，在依从性、接受随机分组或毒性方面均无差异。试验招募仍在继续，以确定阿司匹林是否可以作为一种潜在的低成本、耐受性好的治疗方法，以改善癌症结局。
英国癌症研究中心、英国国家卫生研究院健康技术评估计划、伦敦大学学院 MRC 临床试验单位。
