Local application of sodium thiosulfate as an otoprotectant for cisplatin-exposed patients – A narrative literature review to explore the potential benefit for children with cancer

<h2>Abstract</h2><h3>Background</h3> Ototoxicity is a highly prevalent, serious, and irreversible side effect in cisplatin-treated childhood cancer patients, which can significantly impact speech-language development, psychosocial development, and quality of life. In this respect, the development and implementation of reliable and safe otoprotectants is urgently needed. Sodium thiosulfate (STS*) is an otoprotective drug, recently approved for intravenous administration in cisplatin-treated children with non-disseminated cancer. Intratympanic STS application has been developed as a potential strategy to reduce systemic exposure. To explore potential opportunities for this approach, we have reviewed available literature addressing efficacy, safety, and pharmacokinetics of local STS administration. <h3>Methods</h3> A PubMed search, focused on clinical and pre-clinical efficacy, safety, and pharmacokinetics of local STS application in cisplatin-exposed subjects of all ages was performed. <h3>Findings</h3> From 256 studies, ten studies met the inclusion criteria, including seven preclinical studies, and three clinical studies. Four studies (two preclinical, two clinical) which included pharmacokinetic data, showed that locally administered STS was associated with low systemic serum STS levels. Preclinical studies in guinea pigs showed a significant protective effect on outer hair cell loss or hearing function. However, two clinical trials in adults did not show convincing evidence of otoprotection, by locally administered STS. <h3>Interpretation</h3> Preclinical studies suggest a potential benefit of locally administered STS, however clinical evidence for a significant otoprotective effect is not yet available. The burden and potential sequalae of repeated intratympanic procedures in children, together with the low level of evidence of efficacy, currently limited to pre-clinical data, suggests that further study and potentially improved technology to apply local STS is required for childhood cancer patients receiving cisplatin.