The Effectiveness of Steroids and Antioxidants in the Management of Cisplatin-induced Ototoxicity: A Comprehensive Systematic Review of the Literature and Network Meta-Analysis

Abstract Background: Cisplatin efficacy in cancer therapy is hindered by dose-dependent toxicities, including ototoxicity. Its mechanisms involve cochlear damage and oxidative stress. Gender and age affect susceptibility, with limited treatment options for adults. Objective: To assess the effectiveness of steroids compared to antioxidants (AOs) in preventing and managing cisplatin-induced ototoxicity. Materials and Methods: Data were collected from multiple sources including Medline, CENTRAL, PubMed, and Springer Nature Journals. Adults and pediatrics with the clinical diagnosis of cisplatin-induced ototoxicity, interventional studies (including single-arm studies) were included. Studies with a focus on chemotherapy agents other than cisplatin were excluded. Results: The study encompassed 10 randomized controlled trials spanning 2004–2023 across Canada, Israel, The Netherland, Spain, Turkey, Greece, Italy, and Iran. It aimed to evaluate interventions for preventing cisplatin-induced ototoxicity, including intratympanic injections and oral dietary supplements. Based on the results of this systematic review, thiosulfate-hyaluronate gel showed a 1.3 dB reduction in hearing loss; dexamethasone injections had minimal efficacy; L-N-acetylcysteine (L-NAC) offered significant otoprotection with daily infusion; and transtympanic L-NAC showed no significant benefit. Salicylate usage yielded no decrease in hearing loss. AO dietary supplements showed no difference in results between groups. However, based on the network meta-analysis results, it appears that steroids perform best in reducing cisplatin-induced ototoxicity at higher frequencies (8000 Hz), followed by placebo and then AO. Conclusion: A further molecular and targeted therapy is needed to target the cyto/ototoxic activity and further prevent such deterioration in hearing and promote chemotherapy regime without ototoxic effects.