The Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Am J Gastroenterol. 2011 Jun;106(6):1135-46. doi: 10.1038/ajg.2011.116. Epub 2011 Apr 19.
Subjects in the Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trial (PRESAP/NCT00141193/www.clinicaltrials.gov) were studied to determine efficacy and safety at a year 5 assessment.
In this randomized, placebo-controlled, double-blind trial, 1,561 subjects with diagnosed colorectal adenomas removed within 3 months of the study's initiation were assessed after ~ 3 years on celecoxib followed by 2 years off. Studied in 107 primary and secondary care settings, subjects were stratified by cardioprotective aspirin use and randomized to receive orally 400 ng celecoxib (933 subjects) or placebo (628 subjects) once daily. Efficacy was measured by colonoscopy at years 1, 3, and 5, and safety was measured by investigators for the on-treatment period and collected by subject self-report over 2 years post-treatment.
At year 5, the primary outcome measure was the rate of new adenomas measured cumulatively from baseline. This rate was statistically significantly lower in the celecoxib group (51.4%) than in the placebo group (57.5%; P<0.001). Similarly, the cumulative rate of new advanced adenomas was significantly lower in the celecoxib group (10.0%) than in the placebo group (13.8%; P=0.007). However, the year 5 interval measure, which was not cumulative and did not take the rates of previous years into account, showed that after 2 years off treatment, the celecoxib group (27.0%) was 1.66 times more likely to have new adenomas than the placebo group (16.3%; P<0.0001). Similarly, the percentage of patients with new advanced adenomas was significantly higher in the celecoxib group (5.0%) than in the placebo group (3.8%) (P=0.0072). The evaluation of safety from baseline through year 5 indicated that the risks of serious cardiac disorders (relative risk (RR) 1.66; 95% confidence interval (CI) 1.01-2.73), selected renal/hypertension events (RR 1.35; 95% CI 1.09-1.68), and general vascular (RR 1.34; 95% CI 1.08-1.68) and cardiac disorders (RR 1.59; 95% CI 1.12-2.26) were higher in those taking celecoxib than in those on placebo.
The year 5 cumulative measures of the incidence of new and advanced adenomas were significantly lower in the celecoxib group than in the placebo group, but the year 5 interval rates of these measures were significantly lower in the placebo group than the celecoxib group, perhaps suggesting a release of cyclooxygenase-2 inhibition. Consistent with what has been previously reported, increased risk of renal/hypertension events and cardiac disorders associated with celecoxib therapy mandates caution in patient selection.
对预防结直肠散发性腺瘤（PreSAP）试验（PRESAP/NCT00141193/www.clinicaltrials.gov）中的受试者进行研究，以在 5 年评估时确定疗效和安全性。
在这项随机、安慰剂对照、双盲试验中，在研究开始后约 3 年内接受了结直肠腺瘤切除术的 1561 名受试者，在接受塞来昔布治疗约 3 年后停药 2 年。在 107 个初级和二级保健场所进行研究，根据心脏保护用阿司匹林的使用情况对受试者进行分层，并随机接受口服塞来昔布 400ng（933 名受试者）或安慰剂（628 名受试者），每日一次。在第 1、3 和 5 年通过结肠镜检查测量疗效，在治疗期间由研究者测量安全性，并通过受试者在治疗后 2 年内的自我报告收集安全性数据。
在第 5 年，主要终点是从基线开始累积的新腺瘤发生率。塞来昔布组（51.4%）的这一比率明显低于安慰剂组（57.5%；P<0.001）。同样，塞来昔布组（10.0%）新进展性腺瘤的累积发生率也明显低于安慰剂组（13.8%；P=0.007）。然而，第 5 年的间隔测量结果并非累积性的，也没有考虑前几年的发生率，结果显示，在停止治疗 2 年后，塞来昔布组（27.0%）发生新腺瘤的可能性是安慰剂组（16.3%）的 1.66 倍（P<0.0001）。同样，塞来昔布组（5.0%）的新进展性腺瘤患者比例明显高于安慰剂组（3.8%）（P=0.0072）。从基线到第 5 年的安全性评估表明，严重心脏疾病的风险（相对风险（RR）1.66；95%置信区间（CI）1.01-2.73）、选择的肾脏/高血压事件（RR 1.35；95% CI 1.09-1.68）、一般血管（RR 1.34；95% CI 1.08-1.68）和心脏疾病（RR 1.59；95% CI 1.12-2.26）的风险在服用塞来昔布的患者中高于服用安慰剂的患者。
塞来昔布组的新腺瘤和进展性腺瘤的 5 年累积发生率明显低于安慰剂组，但塞来昔布组的 5 年间隔发生率明显低于安慰剂组，这可能表明环氧化酶-2 抑制作用得到释放。与之前报道的一致，塞来昔布治疗相关的肾脏/高血压事件和心脏疾病风险增加需要谨慎选择患者。
