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Lookup NU author(s): Professor Gareth VealORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Cisplatin-induced hearing loss (CIHL) in pediatric cancer patients is an irreversible and highly prevalent adverse effect with a devastating impact on quality of life. Sodium thiosulfate (STS) has recently been approved for systemic administration as an otoprotective agent in children. However, implementation of systemic STS has its challenges, and there is currently limited evidence to support local STS for children. This review investigates the potential value of locally administered otoprotective agents other than STS with a focus on future pediatric implementation. We conducted a systematic review on the efficacy and safety of locally applied non-STS otoprotective agents in in vivo settings. This included a summary of investigated drug delivery methods and administration routes. We identified 70 preclinical and eight clinical studies. Agents were categorized based on their biological mechanisms: anti-inflammatory, chemical deactivators, calcium blockers, biologicals, and miscellaneous mechanisms. Preclinical studies investigated 45 different agents. Dexamethasone and N-acetylcysteine were identified as efficacious agents recurrently and progressed to clinical trials. Dexamethasone was investigated in three randomized clinical trials (RCTs) and three non-randomized clinical studies and showed statistically significant but not clinically relevant benefit in two trials. N-acetylcysteine was investigated in two clinical trials and one RCT and was minimally effective in the RCT and in one clinical study. Our review did not identify available studies of local alternative otoprotective agents that could reliably replace systemic STS in terms of safety and efficacy for pediatric patients. Further research on the optimal dosage, delivery method, and timing of otoprotective agents is needed.
Author(s): Masroor A, Streefkerk N, Van Grotel M, Geller JI, Ansari M, Bouffet E, Bleyer A, Fresneau B, Sullivan M, Knight K, Kogner P, Maibach R, O'neill AF, Papadakis V, Rajput KM, Brock PR, Veal GJ, Hoetink AE, Huitema ADR, Van Den Heuvel- Eibrink MM
Publication type: Review
Publication status: Published
Journal: Drug Delivery
Year: 2026
Volume: 33
Issue: 1
Online publication date: 01/05/2026
Acceptance date: 23/04/2026
ISSN (print): 1071-7544
ISSN (electronic): 1521-0464
Publisher: Taylor and Francis Ltd.
URL: https://doi.org/10.1080/10717544.2026.2665892
DOI: 10.1080/10717544.2026.2665892
PubMed id: 42068011
Data Access Statement: Data sharing is not applicable to this article as no new data were created or analyzed in this study
