Efficacy of Antioxidant Supplements on Prevention and Amelioration of Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Context: Cisplatin is a widely used antineoplastic agent in the treatment of a wide range of malignancies although it is associated with nephrotoxicity. Much clinical evidence supports the use of antioxidant supplements in the prevention of cisplatin-induced nephrotoxicity (CIN). However, conflicting evidence makes us unable to provide any robust results for antioxidants use against CIN. Objectives:The study aimed to investigate the efficacy of antioxidant supplements on CIN through a comprehensive meta-analysis of randomized controlled trials. Data Sources:A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, CPCI-S (Conference Proceedings Citation Index-Science), ICTRP (International Clinical Trials Registry Platform), and Google Scholar until February 2017 by two independent researchers. Various outcomes such as serum creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine clearance, and incidence of CIN were assessed. All statistical analyses were performed using RevMan V.5.3 Results:Overall, 672 patients were identified from 10 studies of whom 330 (49.10%) patients received antioxidant treatment. Antioxidant treatment showed a significant reduction in serum creatinine (SMD: -3.40, 95% CI: -5.47 to -1.33, P = 0.001), BUN (SMD = -5.96, 95% CI: -10.07 to -1.86, P = 0.004), and eGFR (SMD = -3.77, 95% CI: -6.16 to -1.38; P = 0.002) when compared to the control group.Conclusions: Antioxidant treatment is associated with a reduced risk of CIN. It also has important clinical implications for CIN patients who are not responding to other therapies such as hydration, diuresis, or magnesium supplementation.