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 结肠癌的病变。 这种息肉在高达40%的人身上发现 50岁以上 最近证实，某些非甾体类化合物 抗炎药（NSAID），其抑制前列腺素合成， 可以抑制动物体内息肉和癌症的形成， 粘膜标志物的可重复变化，导致癌症消退 遗传性息肉综合征患者的息肉。 其目的是 建议是确定：1）如果舒林酸（一种NSAID）治疗导致 散在发生的结直肠腺瘤消退，2）如果舒林酸 治疗引起结直肠癌中间标志物的一致变化 癌（PGE_2、BrdU掺入、PCNA），3）检测其可行性 建立一个类似的第三阶段研究的机制， 这个项目的结果。 这项II期研究将是一项随机， 双盲、安慰剂对照试验，2个治疗组，使用 不同的给药方案。 一项合作努力， 临床研究者在大学的丰富经验， 犹他州和基础科学家在 亚利桑那大学使这一建议健全，有效和及时。

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.