Association of Sodium Thiosulfate With Risk of Ototoxic Effects From Platinum-Based Chemotherapy: A Systematic Review and Meta-analysis

IMPORTANCE: Platinum-induced ototoxic effects are a significant issue because platinum-based chemotherapy is one of the most commonly used therapeutic medications. Sodium thiosulfate (STS) is considered a potential otoprotectant for the prevention of platinum-induced ototoxic effects that functions by binding the platinum-based agent, but its administration raises concerns regarding the substantial attenuation of the antineoplastic outcome associated with platinum. OBJECTIVE: To evaluate the association between concurrent STS and reduced risk of ototoxic effects among patients undergoing platinum-based chemotherapy and to evaluate outcomes, including event-free survival, overall survival, and adverse outcomes. DATA SOURCES: From inception through November 7, 2020, databases, including the Cochrane Library, PubMed, Embase, Web of Science, and Scopus, were searched. STUDY SELECTION: Studies enrolling patients with cancer who were undergoing platinum-based chemotherapy that compared ototoxic effects development between patients who received STS and patients who did not and provided adequate information for meta-analysis were regarded as eligible. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. DATA EXTRACTION AND SYNTHESIS: The data were extracted by 2 reviewers independently. A random-effects model was used to explore objectives. MAIN OUTCOMES AND MEASURES: Relative risks (RRs) for ototoxic effects development and hemopoietic event development comparing the experimental group and the control group were estimated. Secondary outcomes were hazard ratios (HRs) for event-free survival and overall survival. Sensitivity analysis and trial sequential analysis were conducted to further consolidate pooled results. RESULTS: Among 4 eligible studies that were included, there were 3 randomized clinical trials and 1 controlled study. A total of 278 patients were allocated to the experimental group (ie, platinum-based chemotherapy plus STS; 158 patients, including 13 patients using contralatral ears of the control group as samples) or the control group (ie, chemotherapy; 133 patients, including 13 patients using contralateral ears of the experimental group as samples). Overall, patients who received STS had a statistically significantly decreased risk of ototoxic effects during the course of platinum-based chemotherapy (RR, 0.61; 95% CI, 0.49-0.77; P < .001; I(2) = 5.0%) without a statistically significant increase in the risk of poor event-free survival (HR, 1.13; 95% CI, 0.70-1.82; P = .61; I(2) = 0%) or overall survival (HR, 1.90; 95% CI, 0.90-4.03; P = .09; I(2) = 0%). In the trial sequential analysis of event-free survival (z = −0.52) and overall survival (z = −1.68), although the cumulative z curves did not surpass the traditional significance boundary (−1.96 to 1.96 for both) or sequential monitoring boundary (event-free survival: −8.0 to 8.0; overall survival boundary not renderable in the analysis because the information size was too small) of the adjusted CI, they did not reach the required information size. CONCLUSIONS AND RELEVANCE: This meta-analysis found that concurrent STS delivery was associated with a decreased risk of platinum-induced ototoxic effects among patients treated with platinum-induced chemotherapy. These findings suggest that concurrent STS for protection against ototoxic effects should be considered for patients indicated for platinum-based chemotherapy.