The Silent Side Effect: Addressing Ototoxicity in Germ Cell Tumor Treatment
Expert Perspectives · Keira Smith · 2026-06-29
Hearing loss from chemotherapy is an underrecognized survivorship problem with real consequences for employment, social life, and mental health. In this interview, Dr. Koral Shah, a Hematology/Oncology Fellow at City Hope, sits down to discuss her team’s randomized phase 1 trial testing whether sodium thiosulfate can reduce cisplatin-induced ototoxicity in adults with metastatic germ cell tumors. As Dr. Shah explains, ototoxicity is not rare, and this trial seeks to translate pediatric success into the adult, metastatic setting.
What Is Ototoxicity?
Dr. Shah defines ototoxicity as inner ear damage caused by certain medications, noting that “upwards of 75% of germ cell tumor patients may develop some degree of hearing loss on audiometry testing after treatment.” She underscores the clinical variability in how patients experience hearing loss: individuals with noisy jobs may detect subtle early changes, while others may not notice deficits until later. Cisplatin’s effect is biological and specific; it damages the outer hair cells within the cochlea, particularly those responsible for higher frequency sounds, often leading to permanent hearing loss or tinnitus.
Intervention and Rationale
The intervention under study is sodium thiosulfate, which is already FDA-approved under the name PEDMARK® to reduce the risk of cisplatin-associated hearing loss in pediatric patients. Given its proposed mechanism—binding reactive platinum species—timing is critical. The drug is given six hours after a patient gets their cisplatin infusion to avoid reducing anticancer efficacy. In the adult germ cell tumor setting, this trial will focus on evaluating safety of using sodium thiosulfate in this population and efficacy of reducing cisplatin-induced ototoxicity.
Study Design
Dr. Shah describes the trial as a randomized comparison between physician-choice cisplatin-based chemotherapy alone and the cisplatin-based chemotherapy followed by sodium thiosulfate administered six hours after each cisplatin dose. The primary endpoint is incidence of clinically meaningful ototoxicity per American Speech-Language-Hearing Associate (ASHA) criteria, with secondary endpoints including high-frequency loss, tinnitus, safety, and progression-free survival. The trial is open and actively enrolling patients at City of Hope, with two patients enrolled so far. Expansion to additional satellite sites is planned to improve access and accrual.
Clinical Implications and Practical Advice
Beyond the trial, Dr. Shah urges clinicians to acknowledge hearing as an essential survivorship metric: “I would encourage clinicians to proactively discuss hearing-related toxicities with patients before they go forward with their chemotherapy, consider audiology assessments, and involve a multidisciplinary supportive care team early on.” Early detection and referral to audiology can mitigate long-term functional impairment.
Conclusion
Designing and activating the trial has been personally meaningful for Dr. Shah: “this was the first clinical trial that I have been part of from design to activation. I think it's been such a wonderful process.” If the adult results mirror pediatric benefit without compromising cancer outcomes, sodium thiosulfate could become a standard tool to preserve hearing and improve quality of life for many survivors.
“Our study reflects the increasing recognition that in germ cell tumor care, cure alone is not the end of the story,” Dr. Shah concludes. “As outcomes continue to improve, survivorship and long-term quality of life are huge considerations that clinicians should have when they’re coming up with treatment plans and choosing their next clinical research endeavor.”
Key Takeaways
Cisplatin-induced ototoxicity is common and impactful, with some studies showing it affects up to 75% of germ cell tumor survivors.
Sodium thiosulfate reduces pediatric ototoxicity and is being tested in adults with metastatic germ cell tumors.
Timing matters; the agent is administered six hours after cisplatin to avoid reducing chemotherapy efficacy.
Early audiology assessment and counseling are recommended: clinicians should proactively discuss hearing related toxicities.
The City of Hope trial is open and enrolling, with plans to expand access to improve accrual and generalizability.
About the Speaker
Koral Shah, MD, is a third-year Hematology/Oncology Fellow at City of Hope Comprehensive Cancer Center. She previously completed her Internal Medicine Residency at Washington University in St. Loius. Dr. Shah’s clinical interests are in genitourinary cancers including germ cell tumors, and her research focuses on survivorship and precision medicine improvements in these diseases.