Veettil Sajesh K, Nathisuwan Surakit, Ching Siew Mooi, Jinatongthai Peerawat, Lim Kean Ghee, Kew Siang Tong, Chaiyakunapruk Nathorn
Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
Clinical Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand,
Cancer Manag Res. 2019 Jan 9;11:561-571. doi: 10.2147/CMAR.S180261. eCollection 2019.
Celecoxib has previously been shown to be effective in reducing recurrent colorectal adenomas, but its long-term effects are unknown. In addition, safety issues are of major concern. Therefore, we examined the efficacy and safety of celecoxib as a chemopreventive agent along with its posttreatment effect.
We performed a meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing celecoxib at various doses (400 mg once daily, 200 mg twice daily, and 400 mg twice daily) vs placebo in persons with history of colorectal adenomas. Several databases were searched from inception up to April 2018. Long-term follow-ups of RCTs were also included to evaluate posttreatment effect. Primary outcome was the incidence of recurrent colorectal adenomas. Various safety outcomes were evaluated, especially cardiovascular (CV) events. Risk-benefit integrated analyses were also performed.
A total of three RCTs (4,420 patients) and three post-trial studies (2,159 patients) were included in the analysis. Use of celecoxib at any dose for 1-3 years significantly reduced the incidence of recurrent advanced adenomas (risk ratio, 0.42 [95% CI, 0.34-0.53]) and any adenomas (0.67 [95% CI, 0.62-0.72]) compared with placebo. Subgroup analysis on different dosing suggested a greater effect with 400 mg twice daily. However, celecoxib 400 mg twice daily significantly increased the risk of serious adverse (1.2 [95% CI, 1.0-1.5]) and CV events (3.42 [95% CI, 1.56-7.46]), while celecoxib at 400 mg/day, especially with once daily dosing, did not increase CV risk (1.01 [95% CI, 0.70-1.46]). Analysis of post-trial studies indicated that the treatment effect disappeared (1.15 [95% CI, 0.88-1.49]) after discontinuing celecoxib for >2 years.
Celecoxib 400 mg once daily dosing could potentially be considered as a viable chemopreventive option in patients with high risk of adenomas but with low CV risk. Long-term trials on celecoxib at a dose of ≤400 mg either once or twice daily are warranted.
先前已证明塞来昔布在减少复发性结肠直肠腺瘤方面有效，但其长期影响尚不清楚。此外，安全性问题备受关注。因此，我们研究了塞来昔布作为化学预防剂的疗效和安全性及其治疗后的效果。
我们基于对随机对照试验（RCT）的系统评价进行了一项荟萃分析，比较了不同剂量（每日一次400毫克、每日两次200毫克和每日两次400毫克）的塞来昔布与安慰剂在有结肠直肠腺瘤病史的人群中的效果。检索了多个数据库，时间跨度从创建到2018年4月。还纳入了RCT的长期随访以评估治疗后的效果。主要结局是复发性结肠直肠腺瘤的发生率。评估了各种安全性结局，尤其是心血管（CV）事件。还进行了风险效益综合分析。
分析共纳入三项RCT（4420例患者）和三项试验后研究（2159例患者）。与安慰剂相比，使用任何剂量的塞来昔布1至3年可显著降低复发性高级别腺瘤（风险比，0.42 [95% CI，0.34 - 0.53]）和任何腺瘤（0.67 [95% CI，0.62 - 0.72]）的发生率。不同剂量的亚组分析表明，每日两次400毫克的效果更佳。然而，每日两次400毫克的塞来昔布显著增加了严重不良事件（1.2 [95% CI，1.0 - 1.5]）和CV事件（3.42 [95% CI，1.56 - 7.46]）的风险，而每日400毫克的塞来昔布，尤其是每日一次给药，并未增加CV风险（1.01 [95% CI，0.70 - 1.46]）。试验后研究分析表明，停用塞来昔布超过2年后治疗效果消失（1.15 [95% CI，0.88 - 1.49]）。
对于腺瘤风险高但CV风险低的患者，每日一次400毫克剂量的塞来昔布可能被视为一种可行的化学预防选择。有必要对每日一次或两次剂量≤400毫克的塞来昔布进行长期试验。
