In male patients with adult-onset germ cell tumors, cisplatin-based chemotherapy may be associated with hearing loss, according to the results of the large, multicenter Platinum Study.
For every 100-mg/m2 increase in cumulative cisplatin dose, a 3.2-dB decline in overall hearing threshold occurred, Robert Frisina, PhD, of the University of South Florida, Tampa, and his associates reported (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2016.66.8822).
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A total of 488 men with adult-onset germ cell tumors who were treated with cisplatin-based chemotherapy were consented into this study, and completed questionnaires concerning neurotoxic symptoms, lifestyle habits, and medication use. Each patient underwent bone-conduction and speech-conducting threshold testing. Pure-tone air conduction thresholds were obtained bilaterally at speech frequency range (0.25 to 12 kHz). Classification of hearing loss and assessment of severity followed standardized criteria as defined by the American Speech-Language-Hearing Association. Median age at cancer diagnosis was 31 years; the median interval between chemotherapy and audiometric testing was 4.25 years. Median cumulative cisplatin dose was 400 mg/m2. Increasing cumulative cisplatin dose was associated with increasing (worse) hearing thresholds at 4 kHz (P = .021), 6 kHz (P = .0017), 8 kHz (P less than .001), 10 kHz (P less than .001), and 12 kHz (P = .0013) after correcting for age.
Cumulative cisplatin doses above 300 mg/m2 were associated with more severe hearing loss, compared with doses less than 300 mg/m2 (odds ratio, 1.59; 95% confidence interval, 1.14-2.21; P = .0066).
Conductive hearing loss in the middle ear was not associated with drug exposure dosage levels. Hypertension was identified as a risk factor for hearing loss as impaired overall hearing threshold was significantly associated with hypertension when correcting for age and cisplatin dose (n = 60, P = .0066).
“Because alterations in the highly successful [germ cell tumor] regimens are unlikely, our results point to the importance of ongoing research aimed at the identification of genetic variants associated with cisplatin-related ototoxicity,” investigators wrote. They also suggested that cancer patients treated with cisplatin should be careful to avoid noise exposure, ototoxic drugs, and other factors that could further increase damage.
This study was funded by the National Cancer Institute. Dr. Frisina reported holding patents related to hearing loss products. Six other investigators reported serving in advisory roles, receiving financial compensation or honoraria from multiple pharmaceutical and biomedical companies.
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