Role of Anti-inflammatory Drugs in the Colorectal Cancer

Abstract

Objective: The objective of this review was to systematically review and synthesize evidence regarding benefits of using nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of colorectal cancer (CRC). Data Sources: The data sources were MEDLINE, PubMed, NEJM, Google Scholar, and Google searches of references from relevant and eligible trials. Review Methods: We screened abstracts and full-text articles of identified references for eligibility and reviewed randomized controlled trials, cohort studies, and meta-analysis for evidence on benefits of using NSAIDs in CRC treatments. For all extracted data, completeness and relevance were checked. Results: The risk of any adenoma among frequent NSAID users was 26.8% vs 39.9% among placebo subjects who later used NSAIDs sporadically (adjusted relative risk = 0.62, 95% confidence interval [CI] = 0.39-0.98; P trend with NSAID use frequency = .03). Long-term use of aspirin reduces the risk of CRC. Aspirin also reduces the incidence of colon adenomas and mortality, especially when used for >10 years. Rofecoxib is associated with the reduction of CRC; however, it was associated with cardiovascular risk (with an overall unadjusted relative risk of 1.50 [95% CI = 0.76-2.94; P = .24]). Adenoma Prevention with Celecoxib trial shows that, for patients of all genotypes, the estimated cumulative incidence of one or more adenomas by year 3 was 59.8% for those randomized to placebo as compared with 43.3% for those randomized to low-dose (200 mg, twice daily) celecoxib (relative risk [RR] = 0.68; 95% CI = 0.59-0.79; P < .001) and 36.8% for those randomized to high-dose (400 mg, twice daily) celecoxib and 60.7% in placebo group (RR = 0.54; 95% CI = 0.46-0.64; P < .001). Conclusions: The use of COX-2 inhibitors both prior to and after diagnosis of CRC seemed to be mildly associated with the reduction in mortality of patients with CRC. Some literatures state that COX-2 inhibitors might play a synergistic role in adjuvant chemotherapy of FOLFOX regimen. Celecoxib was found to increase the radiosensitization of colon cancer cells.

Low serum level of 25‐OH vitamin D relates to Th17 and treg changes in colorectal cancer patients

“…Inflammation also participates in the development of CRC 18,19 . Inflammation can promote tumorigenesis and development by stimulating tumor cell proliferation and the release of inflammatory mediators 20 . CRC patients have immune dysfunction with a Th1/Th2 immune cell imbalance, drifting mainly toward Th2 cells 21 .…”

The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase-2, Promotes Epithelial-Mesenchymal Transition

“…Notably, colorectal adenocarcinoma research has helped understand how the COX-2/PGE2 axis affects carcinogenesis and tumor progression. Sada et al indicates that COX-2/PGE2 overexpression can be observed early in benign lesions like adenomas ( 62 ). Therefore, it seems like the sustained overexpression of the COX-2/PGE2 axis favors adenocarcinoma progression in the context of unresolved chronic inflammation ( 19 ).…”

NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─Structural Modulation, Mechanisms of Action, and Bright Future

“…Several epidemiological and clinical studies supported the potential benefits of NSAIDs in the prevention and treatment of several cancers, including colon, ,, ovarian, breast, , lung, and prostate . In this context, long-term use of aspirin reduces the risk of colorectal, ,− ovarian, , breast, and prostate cancer and hepatocellular carcinoma. , Further, almost 90 clinical trials involving aspirin are being or have been carried out, such as the randomized phase II trial that demonstrated aspirin’s pharmacological efficacy in preventing colorectal cancer in patients at increased risk of colorectal cancer . Thus, the U.S. Preventive Services Task Force (USPSTF) recommended that aspirin can be used to help reduce the risk of cancers including colorectal cancer, although the long-term use of aspirin in older individuals is still being discussed , and needs further confirmation.…”