Local application of otoprotective compounds other than sodium thiosulfate to prevent cisplatin-induced hearing loss: a systematic review
Abstract
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.
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BibTeX
@article{masroor2026local,
title = {{Local application of otoprotective compounds other than sodium thiosulfate to prevent cisplatin-induced hearing loss: a systematic review}},
author = {Amirhossein Masroor and Nienke Streefkerk and Martine van Grotel and James I. Geller and Marc Ansari and Eric Bouffet and Archie Bleyer and Brice Fresneau and Michael Sullivan and Kristin Knight and Per Kogner and Rudolf Maibach and Allison F. O'Neill and Vassilios Papadakis and Kaukab M. Rajput and Penelope R. Brock and Gareth J. Veal and Alexander E. Hoetink and Alwin D. R. Huitema and Marry M. van den Heuvel- Eibrink},
journal = {Drug Delivery},
year = {2026},
month = nov,
doi = {10.1080/10717544.2026.2665892},
url = {https://hal.science/hal-05849844v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Local application of otoprotective compounds other than sodium thiosulfate to prevent cisplatin-induced hearing loss: a systematic review
AU - Amirhossein Masroor
AU - Nienke Streefkerk
AU - Martine van Grotel
AU - James I. Geller
AU - Marc Ansari
AU - Eric Bouffet
AU - Archie Bleyer
AU - Brice Fresneau
AU - Michael Sullivan
AU - Kristin Knight
AU - Per Kogner
AU - Rudolf Maibach
AU - Allison F. O'Neill
AU - Vassilios Papadakis
AU - Kaukab M. Rajput
AU - Penelope R. Brock
AU - Gareth J. Veal
AU - Alexander E. Hoetink
AU - Alwin D. R. Huitema
AU - Marry M. van den Heuvel- Eibrink
PY - 2026
DA - 2026/11/03
JO - Drug Delivery
DO - 10.1080/10717544.2026.2665892
UR - https://hal.science/hal-05849844v1
AB - 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.
SN - 1071-7544
SN - 1521-0464
ER -