Real-World Experience Using Sodium Thiosulfate Pentahydrate Off-Label for Cisplatin Otoprotection in Children, Adolescents, and Young Adults.

Abstract

Background: Cisplatin is used to treat solid tumors but causes irreversible hearing loss. Pedmark, a formulation of sodium thiosulfate (STS), is approved to prevent cisplatin-induced hearing loss (CIHL). Prior to approval, non-Pedmark formulations of STS pentahydrate (STS-P) were prescribed off-label for otoprotection and continue to be used in the absence of data.

Procedure: This multicenter retrospective study examined tolerability, toxicity, and hearing outcomes of STS-P used off-label for otoprotection. Exploratory analyses compared toxicity and hearing data in patients receiving STS-P versus the pre-Pedmark investigational formulation (STS-inv) tested in trials.

Results: Fifty-nine patients received STS-P (16 or 20 g/m²). Infusion-related reactions (IRR) occurred in 14% (8/59), more commonly in patients receiving 20 g/m². No severe adverse events occurred. One patient (2%) discontinued STS-P for IRR. The prevalence of CIHL (International Society of Paediatric Oncology [SIOP] Grade ≥2) at the end of therapy and at the most recent hearing assessment was 30% at both timepoints (12/40 and 8/27, respectively). In exploratory analyses comparing STS-P with STS-inv (n = 14), there was no difference in tolerance or toxicity. In multivariable analysis, a lower risk for CIHL at the end of therapy was found for age ≥5 years, higher dosing of 20 g/m², and received STS-inv (odds ratio 0.02, 95% confidence interval: 0.0003-0.691, p < 0.01). No difference was present at the most recent exam.

Conclusions: STS-P off-label for otoprotection following cisplatin was tolerable in a real-world setting across age groups and cancer types. Formal testing in larger studies of different STS formulations is needed to explore possible differences in toxicity and CIHL prevention.