Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature

Abstract

PURPOSE Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN A comprehensive narrative review is presented. RESULTS Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.

Nuciferine Protects Cochlear Hair Cells from Ferroptosis through Inhibiting NCOA4-Mediated Ferritinophagy

“…To date, there are few clinically approved therapies for preventing cisplatin-induced ototoxicity. Several interventions that have demonstrated strong otoprotective effects in animal experiments, including sodium thiosulfate [ 19 ], dexamethasone [ 20 ], N-Acetylcysteine [ 21 ], amifostine [ 22 ], statins [ 2 ], multivitamins [ 23 ], and D-methionine [ 24 ], have been enrolled in clinical trials. So far, only sodium thiosulfate has been approved by the Food and Drug Administration (FDA) to mitigate cisplatin-induced hearing loss in children.…”

“…So far, only sodium thiosulfate has been approved by the Food and Drug Administration (FDA) to mitigate cisplatin-induced hearing loss in children. However, its application is limited due to its interference with the anti-neoplastic effect of cisplatin and gastrointestinal side effects [ 19 , 25 , 26 ]. Therefore, there is an urgent need to identify novel therapeutic interventions and investigate the underlying molecular mechanisms responsible for cisplatin-induced hearing loss.…”