A Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus after Cisplatin-based Chemotherapy in Survivors of Adult-Onset Cancer

Heather E. Wheeler, Loyola University Chicago

Author Posting © American Society of Clinical Oncology, 2016. This article is posted here by permission of American Society of Clinical Oncology for personal use, not for redistribution. The article was published in J Clin Oncol 34:2712-2720, http://dx.doi.org/10.1200/JCO.2016.66.8822.


Purpose: Cisplatin is widely used, but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer.

Patients and Methods: Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms(0.25-12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association (ASHA) criteria defined hearing loss severity. The geometric mean of hearing thresholds(0.25-12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls.

Results: Increasing cumulative cisplatin dose (median=400 mg/m2; range 200-800) was significantly related to hearing loss at 4, 6, 8, 10 and 12 kHz (P-trends: 0.021-0.00044): every 100 mg/m2 increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4-12 kHz, p=0.00079). Cumulative cisplatin doses >300 mg/m2 were associated with greater ASHA-defined hearing loss severity (OR=1.59, p=0.0066) compared to smaller amounts, doses, and to worse normative-matched quartiles (OR=1.33, p=0.093). Almost 1 in 5 (18%) patients had severe-to-profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (p=6.6 x 10-17). Noise-induced damage (10% patients) was unaffected by cisplatin dose (p=0.59). Hypertension was significantly related(p=0.0066) to overall hearing threshold (4-12 kHz) in age-and cisplatin-dose-adjusted analyses. Middle ear deficits occurred in 22.3% patients, but as expected, were not related to cytotoxic drug dosage.

Conclusion: Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing.