Cimetidine repurposed as a potential immunomodulatory agent against colorectal carcinoma: A systematic review

Abstract

Objective To determine the survival benefit and immunomodulatory effects of cimetidine pre-, peri- or post-operatively in patients with colorectal cancer (CRC). Methods A systematic review was conducted using PubMed and Cochrane Library to retrieve randomized control trials (RCTs) that investigated the effects of cimetidine on survival and immunomodulation via improvement in tumor infiltrating lymphocytes (TILs) and peripheral blood lymphocytes. The review was carried out in accordance with the extended Preferred Reporting Items for Systematic Reviews and Meta-analyses. Results Four studies with the total of 267 patients were included in this systematic review. Treatment duration varied from 5 days to 1 year. Two studies reported a significant TIL response in the resected specimens after administering cimetidine, while one RCT showed an escalation of CD3, CD4 and CD57 lymphocytes in peripheral blood compared to the baseline following cimetidine treatment ( p < 0.01). Of the three trials that examined the effects of cimetidine on survival, only two studies revealed significant survival benefit while the remaining study only showed a trend towards survival benefit. Conclusion Repurposing of existing drugs like cimetidine has a potential to offer a survival benefit by acting as an immunomodulatory agent in patients undergoing curative resection for CRC. However, the heterogeneity seen in current studies and the evolvement of adjunctive therapies for CRC warrant large-scale, well-designed prospective RCTs to establish the efficacy of cimetidine in CRC.