SULINDAC THERAPY FOR SPORADIC COLORECTAL ADENOMAS

结肠癌是美国第二大最常见的恶性肿瘤。 有强有力的证据表明腺瘤性结肠息肉是前驱 结肠癌的病变。高达40%的人会发现这种息肉。 50岁以上。最近证实，某些非类固醇类药物 抑制前列腺素合成的抗炎药(NSAIDs)， 可以抑制动物息肉和癌症的形成，导致 癌症粘膜标志物的可重复性变化和原因消退 遗传性息肉病综合征患者的息肉风险。这样做的目的是 建议确定：1)舒林酸(一种非类固醇抗炎药)治疗是否会导致 散发性结直肠腺瘤的消退，2)舒林酸 治疗引起结直肠中间标志物的持续变化 癌(PGE2，BrdU掺入，增殖细胞核抗原)，3)检查可行性 进行类似的第三阶段研究，并建立机制 这个项目的成果。这项II期研究将是一项随机、 两个治疗组的双盲安慰剂对照试验 不同的给药计划。合作努力结合了 加州大学临床研究人员的丰富经验 和基础科学家在犹他州的杰出成就 亚利桑那大学让这项建议变得合理、高效和及时。

Cancer of the colon is the second most prevalent malignancy in the U.S. There is strong evidence that adenomatous colon polyps are precursor lesions of colon cancer. Such polyps are found in up to 40% of persons over age 50. It has recently been confirmed that certain non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis, can inhibit the formation of polyps and cancers in animals, cause reproducible changes in mucosal markers for cancer and cause regression of polyps in people with genetic polyposis-syndromes. The aims of this proposal are to determine: 1) If therapy with sulindac (a NSAID) causes regression of sporadically occurring colorectal adenomas, 2) If sulindac therapy causes consistent changes in intermediate markers of colorectal cancer (PGE2, BrdU incorporation, PCNA), 3) To examine the feasibility of, and establish the mechanism for, a similar phase III study based on the results of this project. This phase II study is to be a randomized, double blind, placebo-controlled trial with 2 treatment groups using different dosing schedules. A collaborative effort combining the extensive experience of the clinical investigators at the University of Utah and the outstanding achievements of basic scientists at the University of Arizona make this proposal sound, efficient and timely.