Atorvastatin is associated with reduced cisplatin-induced hearing loss
Katharine A. Fernandez, … , Nicole C. Schmitt, Lisa L. Cunningham
Katharine A. Fernandez, … , Nicole C. Schmitt, Lisa L. Cunningham
Published January 4, 2021
Citation Information: J Clin Invest. 2021;131(1):e142616. https://doi.org/10.1172/JCI142616.
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Clinical Research and Public Health Oncology Otology

Atorvastatin is associated with reduced cisplatin-induced hearing loss

Abstract

BACKGROUND Cisplatin is widely used to treat adult and pediatric cancers. It is the most ototoxic drug in clinical use, resulting in permanent hearing loss in approximately 50% of treated patients. There is a major need for therapies that prevent cisplatin-induced hearing loss. Studies in mice suggest that concurrent use of statins reduces cisplatin-induced hearing loss.METHODS We examined hearing thresholds from 277 adults treated with cisplatin for head and neck cancer. Pretreatment and posttreatment audiograms were collected within 90 days of initiation and completion of cisplatin therapy. The primary outcome measure was a change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).RESULTS Among patients on concurrent atorvastatin, 9.7% experienced a CTCAE grade 2 or higher cisplatin-induced hearing loss compared with 29.4% in nonstatin users (P < 0.0001). A mixed-effect model analysis showed that atorvastatin use was significantly associated with reduced cisplatin-induced hearing loss (P ≤ 0.01). An adjusted odds ratio (OR) analysis indicated that an atorvastatin user is 53% less likely to acquire a cisplatin-induced hearing loss than a nonstatin user (OR = 0.47; 95% CI, 0.30–0.78). Three-year survival rates were not different between atorvastatin users and nonstatin users (P > 0.05).CONCLUSIONS Our data indicate that atorvastatin use is associated with reduced incidence and severity of cisplatin-induced hearing loss in adults being treated for head and neck cancer.TRIAL REGISTRATION ClinicalTrials.gov identifier NCT03225157.FUNDING Funding was provided by the Division of Intramural Research at the National Institute on Deafness and Other Communication Disorders (1 ZIA DC000079, ZIA DC000090).

Authors

Katharine A. Fernandez, Paul Allen, Maura Campbell, Brandi Page, Thomas Townes, Chuan-Ming Li, Hui Cheng, Jaylon Garrett, Marcia Mulquin, Anna Clements, Deborah Mulford, Candice Ortiz, Carmen Brewer, Judy R. Dubno, Shawn Newlands, Nicole C. Schmitt, Lisa L. Cunningham

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Figure 2

Atorvastatin use is associated with reduced cisplatin-induced hearing loss.

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Atorvastatin use is associated with reduced cisplatin-induced hearing lo...
Baseline audiometric thresholds were compared with thresholds obtained after cisplatin treatment to determine threshold shifts. (A) In subjects not taking a statin (N = 324 ears), cisplatin treatment resulted in threshold shifts that were more severe at higher frequencies. Subjects taking any statin (N = 219 ears) had significantly less cisplatin-induced hearing loss than subjects who were not taking a statin. Atorvastatin users (N = 97 ears) had significantly less cisplatin-induced hearing loss than nonstatin users. In contrast, cisplatin-induced threshold shifts among simvastatin users (N = 70 ears) were not significantly different from those of nonstatin users. Data represent mean ± SEM, 2-way ANOVA, Dunnett’s multiple-comparison test. (B) Atorvastatin dose was not correlated with high-frequency (6–12.5 kHz) hearing loss. Each dot represents 1 ear. Nonstatin users (N = 324 ears) had 15.9 ± 20.3 dB shifts in high-frequency pure tone average (HF PTA). Atorvastatin users (N = 97 ears) had shifts of 7.8 ± 11.8 dB. There was no correlation between atorvastatin dose and threshold shift. Pearson R correlation. (C) The incidence of cisplatin-induced hearing loss among nonstatin users was 48% per CTCAE criteria. Subjects taking any statin had significantly lower incidence of hearing loss than nonstatin users. The incidence of hearing loss was further reduced among atorvastatin users. Data are percentage of ears per group. Statistical analysis consisted of the χ2 test. (D) Statin use, atorvastatin in particular, was associated with reduced severity of hearing loss. CTCAE criteria were used to categorize the severity of hearing loss. χ2 Analysis showed a significant difference in the distribution of CTCAE hearing loss grades, where the incidence of a grade 2 or higher hearing loss was reduced in statin users compared with nonstatin users. This difference was even greater for atorvastatin users. Data are percentage of ears per group. *P < 0.05, **P < 0.01, ***P < 0.001.