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前驱 结肠癌的病变。大约10%的人会发现这样的息肉 成人，70岁以上的发病率高达50%。它 最近已经证实，某些非类固醇抗炎 抑制环氧合酶和合成环氧合酶的药物(NSAIDs) 前列腺素，可以减少结肠息肉和癌症的形成 被给予已知致癌物质的实验动物。非甾体抗炎药已被报告给 少数患者腺瘤性结肠息肉的消退原因 家族性息肉病和硬纤维样瘤 综合症。最近，非甾体抗炎药吡罗昔康有效地预防了 偶氮甲烷诱导的结肠癌的发生和进展，即使在 直到致癌物暴露后13周才给药。一个明确的剂量- 吡罗昔康的反应关系得到了令人信服的证明， 即使在测试的最低剂量下，肿瘤抑制也很明显。我们有 证明每天服用20毫克和10毫克吡罗昔康 显著降低慢性前列腺炎患者直肠黏膜前列腺素E_2含量 腺瘤性结肠息肉。初步结果表明，更低的 剂量的吡罗昔康可能会显著影响结肠粘膜，反映在 抑制PGE2含量。重要的是要确定是否 显示低剂量的短期效果在延长时间内持续 治疗，患者是否会遵守，以及药物方面 在这个低剂量下就会产生影响。这一拟议阶段IIb的理由 这项研究源于吡罗昔康在 在动物模型中预防结肠癌及其临床应用的必要性 使用与正常使用剂量不同且剂量较低的药物的经验 用于治疗人类疾病，并记录所使用的剂量 对结肠粘膜有持续作用。

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.