CALCIUM AND ASPIRIN PREVENTION TRIAL

描述（改编自研究者摘要）：修改 膳食补充剂和药物的致癌过程 是结肠癌预防研究的重点。两个顺序 建议进行研究以调查钙和 阿司匹林补充剂在结肠癌化学预防中的应用两种药剂 选择这些研究是因为（a）广泛的流行病学和实验室数据 支持其化学预防潜力，（B）其安全性特征具有 在其他健康状况下， （c）它们可能具有互补的作用机制，以及（d） 研究小组对这些药剂有相当丰富的经验。目标 人群将是既往有散发性 入组5年内结肠腺瘤性息肉，无病史 之前的恶性肿瘤初步的2a期试验旨在 确定阿司匹林的最小剂量， 活动随后的随机、双盲、安慰剂对照 2b期试验旨在测试单药和联合用药 阿司匹林和钙的化学预防作用，给予12周。的 阿司匹林的剂量将在2a期试验中确定， 剂量将是先前证明的有效剂量2000 mg/d。 主要终点为结肠粘膜前列腺素E2水平， PCNA法测定上皮细胞增殖指数。的 研究人员假设，钙和阿司匹林将有一个 对结肠粘膜的协同、风险降低作用， 有腺瘤性息肉病史本研究将在 胃肠病学家网络，可接触大量 腺瘤性息肉患者和化学预防的丰富经验 审判2b期研究的数据将用于构建3期研究。 复发性息肉的研究

DESCRIPTION (Adapted from the investigator's abstract): Modification of the carcinogenic process by dietary supplements and pharmacologic agents is a major emphasis in colon cancer prevention research. Two sequential studies are proposed to investigate the role of combined calcium and aspirin supplementation in colon cancer chemoprevention. The two agents are chosen because (a) extensive epidemiologic and laboratory data support their chemopreventive potential, (b) their safety profile has been well delineated in other health conditions in which they are of benefit, (c) they may have complementary mechanisms of action, and (d) the research team has considerable experience with these agents. Target populations will be subjects with a prior history of sporadic adenomatous polyps of the colon within 5 years of entry and no history of previous malignancy. A preliminary Phase 2a trial is designed to determine the minimum dose of aspirin which has relevant biologic activity. A subsequent randomized, double-blind, placebo controlled Phase 2b trial is designed to test the single and combined chemopreventive effects of aspirin and calcium, given for 12 weeks. The aspirin dose will be determined in the phase 2a trial, and the calcium dose will be the previously demonstrated effective dose of 2000 mg/d. The primary endpoints will be colonic mucosal prostaglandin E2 levels and epithelial proliferation indices measured by PCNA methodology. The investigators hypothesize that calcium and aspirin will have a synergistic, risk reducing effect on the colonic mucosa in subjects with a history of adenomatous polyps. The study will be performed in a network of gastroenterologists with access to a large population of adenomatous polyp patients and extensive experience in chemoprevention trials. Data from the phase 2b study will serve to construct a phase 3 study on recurrent polyps.