Secondary chemoprevention of Barrett's esophagus with celecoxib: Results of a randomized trial
Secondary chemoprevention of Barrett's esophagus with celecoxib: Results of a randomized trial
复制标题
DOI：
10.1093/jnci/djk112
复制
发表时间：
2007-04-04
期刊：
影响因子：
--
通讯作者：
Forastiere, Arlene A.
中科院分区：
文献类型：
--
作者：
Heath, Elisabeth I.;Canto, Marcia Irene;Forastiere, Arlene A.
Barrett食管是一种恶性前病变，是发展为食管腺癌的危险因素，其发病率正在迅速增加。由于阿司匹林和其他非甾体抗炎药，如塞来昔布，可能会降低患食管癌的风险，我们研究了长期服用塞来昔布对Barrett食管发育不良患者的影响。方法化学预防Barrett食管试验（CBET）是一项多中心随机安慰剂对照试验，使用塞来昔布治疗Barrett食管和低级别或高级别发育不良患者。患者随机接受200毫克塞来昔布或安慰剂治疗，每日口服两次，然后按发育不良程度分层。主要结局是塞来昔布组和安慰剂组从基线到治疗48周时活检样本中不典型增生比例的变化。二级和三级结局包括组织学变化和相关生物标志物表达水平的评估。所有统计检验均为双侧检验。结果从2000年4月1日至2003年6月30日，222例患者注册到CBET，其中100例低级别或高级别巴雷特发育不良患者随机分配到治疗组（塞来昔布组49例，安慰剂组51例）。治疗48周后，在低级别（塞来昔布组中位变化= -0.09，四分位数范围[IQR] = -0.32至0.14，安慰剂组中位变化= -0.07,IQR = -0.26至0.12，P= 0.64）和高级别（塞来昔布组中位变化= 0.12,IQR = -0.31至0.55，安慰剂组中位变化= 0.02,IQR = -0.24至0.28，P= 0.88）分层中，不同治疗组活检样本中不典型增生或癌症的比例变化均无差异。Barrett食管总表面积差异无统计学意义；前列腺素水平；环氧化酶1/2 mRNA水平；与安慰剂相比，塞来昔布组在肿瘤抑制基因p16、大肠腺瘤性息肉病和e -钙粘蛋白甲基化方面的差异显著。结论：每日2次给予200 mg塞来昔布治疗48周，似乎不能阻止巴雷特发育不良向癌症发展。
Background Barrett's esophagus is a premalignant condition that is a risk factor for the development of esophageal adenocarcinoma, a disease whose incidence is rapidly increasing. Because aspirin and other nonsteroidal anti-inflammatory drugs, such as celecoxib, may decrease the risk of developing esophageal cancer, we investigated the effect of long-term administration of celecoxib in patients with Barrett's esophagus with dysplasia.Methods Chemoprevention for Barrett's Esophagus Trial (CBET) is a phase Ilb multicenter randomized placebo-controlled trial of celecoxib in patients with Barrett's esophagus and low- or high-grade dysplasia. Patients were randomly assigned to treatment with 200 mg of celecoxib or placebo, both administered orally twice daily, and then stratified by grade of dysplasia. The primary outcome was the change from baseline to 48 weeks of treatment in the proportion of biopsy samples with dysplasia between the celecoxib and placebo arms. Secondary and tertiary outcomes included evaluation of changes in histology and expression levels of relevant biomarkers. All statistical tests were two-sided.Results From April 1, 2000, through June 30, 2003, 222 patients were registered into CBET, and 100 of them with low or high-grade Barrett's dysplasia were randomly assigned to treatment (49 to celecoxib and 51 to placebo). After 48 weeks of treatment, no difference was observed in the median change in the proportion of biopsy samples with dysplasia or cancer between treatment groups in either the low-grade (median change with celecoxib = -0.09, interquartile range [IQR] = -0.32 to 0.14 and with placebo = -0.07, IQR = -0.26 to 0,12; P=.64) or high-grade (median change with celecoxib = 0.12, IQR = -0.31 to 0.55, and with placebo = 0.02, IQR = -0.24 to 0.28; P=.88) stratum. No statistically significant differences in total surface area of the Barrett's esophagus; in prostaglandin levels; in cyclooxygenase-1/2 mRNA levels; or in methylation of tumor suppressor genes p16, adenomatous polyposis coli, and E-cadherin were found with celecoxib compared with placebo.Conclusions Administration of 200 mg of celecoxib twice daily for 48 weeks of treatment does not appear to prevent progression of Barrett's dysplasia to cancer.