Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Cancer Prev Res (Phila). 2011 May;4(5):655-65. doi: 10.1158/1940-6207.CAPR-11-0106.
Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin--mean 3.8 mm versus 5.5 mm for patients treated 1 or more years (adjusted P = 0.09) and mean 3.0 mm versus 6.0 mm for patients treated more than 1 year (P = 0.02); there were similar weaker trends with RS versus non-RS. Exploratory translational endpoints included crypt length (which was significantly shorter in normal-appearing mucosa in the RS group over time) and laboratory measures of proliferation (including Ki67). This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load (number and size) with 600 mg of aspirin daily. RS had no clinical effect on adenomas.
支持阿司匹林和抗性淀粉 (RS) 预防结直肠癌的证据来自于流行病学和实验室研究（阿司匹林和 RS）以及随机对照临床试验（阿司匹林）。家族性腺瘤性息肉病 (FAP) 侵袭年轻人，如果不治疗，几乎会导致 100%的结直肠癌和早逝风险。我们进行了一项国际性、多中心、随机、安慰剂对照的临床试验，研究了阿司匹林（600mg/d）和/或 RS（30g/d）用于预防 10 至 21 岁 FAP 患者疾病进展的情况，为期 1 至 12 年。采用 2×2 析因设计，患者被随机分配到以下四个研究组：阿司匹林加 RS 安慰剂；RS 加阿司匹林安慰剂；阿司匹林加 RS；RS 安慰剂加阿司匹林安慰剂；他们接受了标准的年度临床检查，包括内窥镜检查。主要终点是直肠和乙状结肠的息肉数量（干预结束时），主要次要终点是最大息肉的大小。共有 206 名随机分配的 FAP 患者开始接受干预，其中 133 名至少有一次随访内窥镜检查，因此纳入主要分析。两种干预措施均未显著减少直肠和乙状结肠的息肉数量：阿司匹林相对风险 = 0.77（95%CI，0.54-1.10；与非阿司匹林组相比）；RS 相对风险 = 1.05（95%CI，0.73-1.49；与非 RS 组相比）。与非阿司匹林组相比，接受阿司匹林治疗的患者的最大息肉大小呈缩小趋势——治疗 1 年或以上的患者平均为 3.8 毫米，而治疗 1 年以上的患者平均为 5.5 毫米（调整后 P=0.09）；与非 RS 组相比，也存在类似的较弱趋势。探索性转化终点包括隐窝长度（RS 组在正常外观黏膜中随时间推移而显著缩短）和增殖的实验室测量（包括 Ki67）。这项临床试验是 FAP 背景下进行的最大规模临床试验，发现每天服用 600mg 阿司匹林可降低息肉负荷（数量和大小）。RS 对腺瘤没有临床作用。
