# Prevention of Cisplatin-induced Hearing Loss in Children with Cancer

> **NIH NIH K23** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2021 · $48,074

## Abstract

Cisplatin is used in the treatment of many childhood cancers including brain, bone, germ cell, liver, and
peripheral nervous tumors; together, these cancers constitute nearly 40% of the childhood cancers diagnosed
each year. While effective for cure, cisplatin causes severe, permanent, and progressive hearing loss from
theorized free-radical damage to the cochlea. This, in turn, results in debilitating neurocognitive deficits and
impacts the quality of life for childhood cancer survivors. Current strategies to protect hearing are ineffective,
toxic, unsafe, or inadequate. The scientific objective of this proposal is to address this need by transitioning
the promising new otoprotectant drug N-acetylcysteine (NAC) into clinical trials. Pre-clinical evidence for NAC
demonstrates the potential for greater efficacy than previously tested agents without compromising cisplatin
efficacy. We therefore propose to test NAC in an early phase clinical trial for children receiving cisplatin to
evaluate dose, toxicity, and any signs of interference with chemotherapy efficacy (Aim 1). Supporting
laboratory aims on the proposed trial will provide new insight into the intersection of pharmacogenomics,
pharmacokinetics, and the mechanisms of ototoxicity and otoprotection (Aim 2). Evidence for successful
hearing protection will be explored through comparison to a non-NAC treated cohort and via comprehensive
post-treatment physiological and behavioral hearing assessments in survivors (Aim 3). The richness of data
derived from the trial will provide the basis for a subsequent Phase III trial testing efficacy as an otoprotectant.
 The training objectives embedded within the clinical trial will foster Dr. Orgel’s growth as a clinical
investigator in cancer control focused on translational research for otoprotection. Using a combination of
classroom and hands-on experience, the study will promote his proficiency with (1) study design questions
surrounding otoprotection, (2) laboratory models of otoprotection and ototoxicity, and (3) audiology physiology
and assessment. Dr. Orgel has access to a rich academic research environment, one of the largest pediatric
oncology populations in the country, the support of his institution, and a mentorship team of renowned experts.
Dr. Freyer, with extensive expertise in otoprotection in cancer trials will lead the mentoring committee
consisting of (1) Dr. Neuwelt – xenograft models of ototoxicity and thiol otoprotection, including the laboratory
development of NAC, (2) Dr. Eisenberg – pediatric clinical and research audiology, and representing access to
the combined wealth of audiology expertise at the USC Caruso Family Center for Childhood Communication,
and (3) Dr. Wayne (the Division Head for Dr. Orgel) – general translational research involving biological
targets. While all mentors have long track records of mentorship, Drs. Freyer and Wayne will be primarily
responsible to guide Dr. Orgel’s achievement of the milestones necessar...

## Key facts

- **NIH application ID:** 10447944
- **Project number:** 3K23DC014291-05S1
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Etan Orgel
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $48,074
- **Award type:** 3
- **Project period:** 2016-07-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447944

## Citation

> US National Institutes of Health, RePORTER application 10447944, Prevention of Cisplatin-induced Hearing Loss in Children with Cancer (3K23DC014291-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10447944. Licensed CC0.

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