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BMJ. 2016 Dec 5;355:i6188. doi: 10.1136/bmj.i6188.

Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis.

Author information

1
Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
2
Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA sis040@ucsd.edu.
3
Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.
4
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
5
Department of Library Services, Mayo Clinic, Rochester, MN, USA.
6
Divison of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
7
Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
8
Moores Cancer Center, University of San Diego, La Jolla, CA, USA.
9
Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.

Abstract

OBJECTIVE:

 To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis.

DATA SOURCES:

 Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries.

STUDY SELECTION:

 Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events.

DATA EXTRACTION:

 Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria.

RESULTS:

 15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated.

CONCLUSIONS:

 Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile.

REGISTRATION:

 PROSPERO (CRD42015029598).

PMID:
27919915
PMCID:
PMC5137632
DOI:
10.1136/bmj.i6188
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: PSD and EM are supported by the NIDDK training grant 5T32DK007202. SS is supported by the NIH/NLM training grant T15LM011271 and the American College of Gastroenterology junior faculty development award. SG is partly supported by NCI 2 U54CA132379-06A1, as well as merit review award No 1 I01 HX001574-01A1 from the US Department of Veterans Affairs Health Services Research and Development Service of the VA Office of Research and Development. The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs.

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