Lower, more frequent cisplatin dosing minimizes hearing loss in head and neck cancer
Katharine A. Fernandez, … , Nicole C. Schmitt, Lisa L. Cunningham
Katharine A. Fernandez, … , Nicole C. Schmitt, Lisa L. Cunningham
Published October 22, 2025
Citation Information: JCI Insight. 2025;10(20):e196230. https://doi.org/10.1172/jci.insight.196230.
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Clinical Research and Public Health Clinical Research Oncology

Lower, more frequent cisplatin dosing minimizes hearing loss in head and neck cancer

Abstract

BACKGROUND Cisplatin is often the cytotoxic drug of choice for chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC), but it can lead to irreversible hearing loss. There may be similar oncologic outcomes but different toxicity profiles depending on whether cisplatin is given at 75–100 mg/m2 every 3 weeks or 30–40 mg/mg2 weekly. This study compares cisplatin-induced hearing loss in patients with HNSCC receiving similar cumulative doses of cisplatin administered either on higher-dose or lower-dose treatment schedules.METHODS Using the Enhancing Cancer Hearing Outcomes (ECHO) dataset from 5 academic centers, we conducted a multicenter retrospective cohort study of adults (≥18 years) with HNSCC receiving cisplatin-based CRT. Participants were grouped by cisplatin dose schedule: every 3 weeks (≥75 mg/m²) or weekly (<75 mg/m²). Hearing loss was assessed using American Speech-Language-Hearing Association (ASHA) and Common Terminology Criteria for Adverse Events (CTCAE) v5.0 threshold shift criteria based on audiograms obtained ≤120 days before and after treatment. Risk differences and predictors of hearing loss were evaluated using χ2 analyses and multivariate regression. Kaplan-Meier curves assessed overall and disease-free survival.RESULTS Among 564 participants (1,127 ears), lower-dose weekly cisplatin was associated with significantly lower incidence of hearing loss (ASHA criteria: 57% vs. 82%; CTCAE criteria: 39% vs. 69%). CTCAE grade ≥2 hearing loss occurred in 18% of the weekly group versus 50% of the 3-week group. Multivariate analysis confirmed treatment schedule as an independent predictor of ototoxicity. Two-year survival outcomes did not differ between groups.CONCLUSIONS Weekly low-dose cisplatin significantly reduced the incidence and severity of hearing loss without compromising survival, supporting its broader use in CRT for HNSCC.

Authors

Katharine A. Fernandez, Abu S. Chowdhury, Amanda Bonczkowski, Paul D. Allen, Maura H. Campbell, David S. Lee, Charvi Malhotra, Brandi R. Page, Deborah A. Mulford, Candice Evita Ortiz, Peter L. Santa Maria, Peter Kullar, Saad A. Khan, Shawn D. Newlands, Nicole C. Schmitt, Lisa L. Cunningham

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Figure 4

Weekly administration of cisplatin significantly reduces the risk of developing a clinically meaningful cisplatin-induced hearing loss.

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Weekly administration of cisplatin significantly reduces the risk of dev...
Analysis of the incidence of a CTCAE grade ≤1 hearing loss for the full cohort and different subgroups. For the overall cohort and the subgroups, the difference in the incidence (%) and 95% CIs were estimated using a stratified risk difference analysis. Significant differences (red diamonds) in the calculated incidence of a hearing loss (HL) were observed for the full cohort, as well as for the male and female subgroups; individuals 50–59 and 60–69 years; individuals receiving total cumulative cisplatin doses 100–199 and 200–299 mg/m2; and for those with normal hearing and mild hearing loss at baseline. Red indicates significant P values.