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.
Subject(s)
Cimetidine , Colorectal Neoplasms , Randomized Controlled Trials as Topic , Humans , Cimetidine/therapeutic use , Cimetidine/pharmacology , Colorectal Neoplasms/drug therapy , Drug Repositioning , Immunomodulating Agents/pharmacology , Immunomodulating Agents/therapeutic use , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunologyABSTRACT
OBJECTIVE: Adverse Drug Reactions (ADR) add a significant clinical and economic burden to the healthcare system of a country. We present an overview of the different approaches of ADR reporting systems worldwide and their evolution over time. METHODS: A systematic review of the literature was made based on PubMed and the Cochrane database of systematic reviews. The articles searched for included original articles, WHO and FDA reports and institute of medicine reports. Reporting ADRs is the cornerstone of detecting uncommon ADRs once the drugs are on the market. In many countries, ADR reporting is regulated by national regulatory bodies and various methods are employed to report ADRs. Direct reporting by healthcare professionals has been adopted by many developed and developing countries. With emerging new technologies in the field of medicine, there is a great potential to develop better ADR reporting systems in the countries where they have poor reporting. CONCLUSION: Development and acquisition of newer technologies to promote ADR monitoring and reporting is a necessity for an effective pharmacovigilance system in a country.
