Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.
Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.
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DOI：
10.1016/s0140-6736(11)61049-0
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发表时间：
2011-12-17
期刊：
影响因子：
168.9
通讯作者：
Bishop, D. Timothy
中科院分区：
文献类型：
--
作者：
Burn, John;Gerdes, Anne-Marie;Macrae, Finlay;Mecklin, Jukka-Pekka;Moeslein, Gabriela;Olschwang, Sylviane;Eccles, Diane;Evans, D. Gareth;Maher, Eamonn R.;Bertario, Lucio;Bisgaard, Marie-Luise;Dunlop, Malcolm G.;Ho, Judy W. C.;Hodgson, Shirley V.;Lindblom, Annika;Lubinski, Jan;Morrison, Patrick J.;Murday, Victoria;Ramesar, Raj;Side, Lucy;Scott, Rodney J.;Thomas, Huw J. W.;Vasen, Hans F.;Barker, Gail;Crawford, Gillian;Elliott, Faye;Movahedi, Mohammad;Pylvanainen, Kirsi;Wijnen, Juul T.;Fodde, Riccardo;Lynch, Henry T.;Mathers, John C.;Bishop, D. Timothy
观察性研究报告说，经常服用阿司匹林的人患结肠直肠癌的几率降低。随机对照试验显示腺瘤的风险降低，但没有一项将预防结直肠癌作为主要终点。CAPP 2试验旨在研究阿司匹林和抗性淀粉对Lynch综合征（遗传性结直肠癌的主要形式）携带者的抗肿瘤作用;我们现在报告随机分配到阿司匹林或安慰剂组的参与者的长期随访。在CAPP 2随机试验中，Lynch综合征携带者被随机分配到600 mg阿司匹林或阿司匹林安慰剂或30 g抗性淀粉或淀粉安慰剂组，为期4年。随机分组为16人一组，提供可选的单药随机分组和延长的干预后双盲随访;参与者和研究者对治疗分配不知情。主要终点是结直肠癌的发展。按意向治疗和符合方案进行分析。本试验已注册，ISRCTN 59521990。861名参与者被随机分配到阿司匹林或阿司匹林安慰剂组。在平均55.7个月的随访中，48名参与者发生了53例原发性结直肠癌（427例中的18例随机分配到阿司匹林组，434例中的30例服用阿司匹林安慰剂）。对首次结直肠癌发生时间的意向治疗分析显示风险比（HR）为0.63（95%CI 0.35 - 1.13，p= 0.12）。考虑多个主要事件的Poisson回归得出的发生率比（IRR）为0.56（95%CI 0.32 - 0.99，p= 0.05）。对于完成2年干预的参与者（258例阿司匹林，250例阿司匹林安慰剂），符合方案分析得出HR为0.41（0.19 - 0.86，p= 0.02），IRR为0.37（0.18 - 0.78，p= 0.008）。干预后没有不良事件的数据;在干预期间，阿司匹林组和安慰剂组的不良事件没有差异。在遗传性结直肠癌携带者中，每天服用600 mg阿司匹林，平均25个月，55.7个月后，癌症发病率显著降低。需要进一步的研究来确定阿司匹林治疗的最佳剂量和持续时间。欧洲联盟;英国癌症研究所;拜耳公司;国家淀粉和化学公司;英国医学研究理事会;纽卡斯尔医院受托人;澳大利亚维多利亚癌症理事会; THRIPP南非;芬兰癌症基金会; SIAK瑞士;拜耳制药。
Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95% CI 0·35–1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95% CI 0·32–0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19–0·86, p=0·02) and an IRR of 0·37 (0·18–0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma.