Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

Abstract

BackgroundProtective effects of several chemopreventive agents (CPAs) against colorectal adenomas have been well documented in randomized controlled trials (RCTs); however, there is uncertainty regarding which agents are the most effective.MethodsWe searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA) of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome). Using NMA, we ranked CPAs based on efficacy.ResultsWe identified 20 eligible RCTs enrolling 12,625 participants with a history of colorectal cancer or adenomas who were randomly assigned to receive either a placebo or one of 12 interventions. NMA using all trials demonstrated that celecoxib 800 mg/day (relative risk [RR] 0.61, 95% confidence interval [CI] 0.45–0.83), celecoxib 400 mg/day (RR 0.70, 95% CI 0.55–0.87), low-dose aspirin (RR 0.75, 95% CI 0.59–0.96) and calcium (RR 0.81, 95% CI 0.69–0.96) were significantly associated with a reduction in the recurrence of any adenomas. NMA results were consistent with those from pairwise meta-analysis. The evidence indicated a high (celecoxib), moderate (low-dose aspirin) and low (calcium) Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality. NMA ranking showed that celecoxib 800 mg/day and celecoxib 400 mg/day were the best CPAs, followed by low-dose aspirin and calcium. Considering advanced adenoma recurrence, only celecoxib 800 mg/day and celecoxib 400 mg/day were demonstrated to have a protective effect (RR 0.37, 95% CI 0.27–0.52 vs RR 0.48, 95% CI 0.38–0.60, respectively).ConclusionThe available evidence from NMA suggests that celecoxib is more effective in reducing the risk of recurrence of colorectal adenomas, followed by low-dose aspirin and calcium. Since cyclooxygenase-2 (COX-2) inhibitors (eg, celecoxib) are associated with important cardiovascular events and gastrointestinal harms, more attention is warranted toward CPAs with a favorable benefit-to-risk ratio, such as low-dose aspirin and calcium.

Efficacy and safety of chemopreventive agents on colorectal cancer incidence and mortality: systematic review and network meta-analysis

“… 70 It should be noted that low dose (400 IU/day) of vitamin D was used in all primary prevention trials (and not in the form of vitamin D3). 69 , 71 As a result, future trials of vitamin D may need to explore both different forms and various dosing of vitamin D.…”

Vicenin-2 inhibits Wnt/β-catenin signaling and induces apoptosis in HT-29 human colon cancer cell line

“…MTT assay was used to determine cell viability as described previously. 14 Briefly, cells were seeded at a density of 1×10 4 cells/well in a 24-well plate and cultured in a serum-free DMEM for 16 hours. The cells were then treated with Vicenin-2 in serial concentrations (0, 3.12, 6.24, 12.5, 25, 50, 100, and 150 µM) for 24 or 48 hours.…”

Low‐dose aspirin can reduce colorectal cancer mortality after surgery: A 10‐year follow‐up of 13 528 colorectal cancer patients

“…18 A recent metaanalysis also confirmed that COX-2 inhibitor, low-dose aspirin, and calcium can reduce the incidence of recurrent adenoma. 19 In this study, we found that in patients who had already been diagnosed with CRC and undergone surgery, even at a low-dose aspirin of 80 mg, the cancer preventive effect is evident. This is in keeping with the aforementioned pooled analysis by Rothwell et al, which showed that daily aspirin of at least 75 mg reduced the 20-year risk of colon cancer.…”

“…On the other hand, an RCT combining aspirin with calcitriol and calcium failed to show any effect in the reduction of recurrent adenoma . A recent meta‐analysis also confirmed that COX‐2 inhibitor, low‐dose aspirin, and calcium can reduce the incidence of recurrent adenoma …”