CANCER PREVENTION--PIROXICAM EFFECTS ON COLON MUCOSA

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。 这种息肉在大约10%的 成年人，发病率在70岁以上的人中高达50%。 它 最近证实某些非甾体抗炎药 药物（非甾体抗炎药），抑制环氧合酶和合成 前列腺素，可以减少结肠息肉和癌症的形成， 给实验动物注射已知的致癌物质。 据报道，NSAID 导致少数患者腺瘤性结肠息肉消退 家族性息肉病和加德纳氏病患者的硬纤维瘤 综合征 最近，NSAID吡罗昔康有效地预防了 氧化偶氮甲烷诱导的结肠癌的发展和进展，即使当 在致癌物暴露后13周进行。 很明显的剂量- 令人信服地证明了吡罗昔康的反应关系， 即使在最低的测试剂量下肿瘤抑制也是明显的。 我们有 证明每日20 mg和10 mg吡罗昔康治疗 显著降低直肠粘膜PGE 2含量 结肠腺瘤性息肉 初步结果表明，即使是低 吡罗昔康的剂量可显著影响结肠粘膜， 抑制PGE 2含量。 重要的是要确定 证明低剂量的短期效应在长期 治疗，患者是否会遵守这些，以及是否有药物副作用 在这种低剂量下会产生效果。 拟定的第IIb阶段的基本原理 研究源自吡罗昔康在以下方面的已证实有效性： 在动物模型中预防结肠癌， 与正常使用的药物剂量不同且剂量较低的经验 用于治疗人类疾病，并记录所用剂量 对结肠粘膜造成持续影响。

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 approximately 10% of adults, with incidence increasing to as high as 50% in persons over 70. it has recently been confirmed that certain nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase and the synthesis of prostaglandins, can reduce formation of both colon polyps and cancers in experimental animals given known carcinogens. NSAIDs have been reported to cause regression of adenomatous colon polyps in a small number of patients with familial polyposis and of desmoid tumors in persons with Gardner's syndrome. Most recently, the NSAID piroxicam effectively prevented development and progression of azoxymethane-induced colon cancer, even when administered as late as 13 weeks after carcinogen exposure. A clear dose- response relationship was convincingly demonstrated for piroxicam, with tumor suppression apparent at even the lowest dose tested. We have demonstrated that treatment with 20mg and 10mg piroxicam daily significantly reduces PGE2 content of rectal mucosa in patients with adenomatous colon polyps. Preliminary results suggest that even lower doses of piroxicam may significantly affect colon mucosa as reflected by suppression of PGE2 content. It will be important to determine whether the demonstrated short term effect of a low dose persists during prolonged therapy, whether patients will comply with such, and whether drug side effects occur at this low dose. The rationale for this proposed phase IIb study is derived from the demonstrated effectiveness of piroxicam in preventing colon cancer in animal models and the need to gain clinical experience with a different and lower dose of the drug than normally used in treatment of human disease, and to document that the dose employed causes a sustained effect on colon mucosa.