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Cisplatin kills the hair cells of the inner ear, starting at the high frequencies, and the loss does not come back. In children, sodium thiosulfate given six hours after each dose cut hearing loss from 63 to 33 per cent in one randomised trial and from 56.4 to 28.6 per cent in another. Nothing equivalent is licensed for adults.
Cisplatin ototoxicity is permanent, bilateral and dose-related, and it begins in the frequencies above the speech range, which is why it is often missed unless hearing is tested. Carboplatin is much less ototoxic at standard doses. Tinnitus commonly accompanies it.
The protective agent is sodium thiosulfate, given as a short infusion six hours after the cisplatin so that it clears the drug from the bloodstream without reaching the tumour during the window in which cisplatin is working. Two randomised trials in children established it. In SIOPEL 6, in standard-risk hepatoblastoma, hearing loss of Brock grade 1 or higher occurred in 18 of 55 children (33 per cent) given cisplatin with sodium thiosulfate against 29 of 46 (63 per cent) given cisplatin alone, a relative risk of 0.52 (95 per cent confidence interval 0.33 to 0.81), with three-year event-free survival of 82 against 79 per cent and overall survival 98 against 92 per cent. In the Children's Oncology Group trial ACCL0431, across a range of cisplatin-treated cancers, hearing loss occurred in 14 of 49 (28.6 per cent) against 31 of 55 (56.4 per cent) in the control group.
The approved indication reflects a caution rather than an oversight. The United States label for sodium thiosulfate states that it "is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors", with a limitation of use that safety and efficacy "have not been established when administered following cisplatin infusions longer than 6 hours" because "irreversible ototoxicity may have already occurred".
Adults receive most of the world's cisplatin and have none of this. In 1,422 adult-onset cancer survivors in the Platinum Study, audiometrically assessed ototoxicity affected 1,061, or 75 per cent, and was related to cumulative cisplatin dose, reduced kidney function, high blood pressure and age. In an earlier analysis of 488 men treated for germ cell tumours, every additional 100 milligrams per square metre of cisplatin produced a 3.2 decibel impairment in age-adjusted hearing threshold, 18 per cent had severe to profound hearing loss, and 40 per cent had tinnitus. A systematic review of eight adult trials of otoprotectants, 431 patients in total, found hearing loss in 63.3 per cent of treated patients against 66.2 per cent of controls, no difference. A 2023 review of practice concluded that there is "a lack of standardized guidelines for monitoring and treatment of cisplatin-induced ototoxicity, especially in the adult cancer patient population".
The practical measures for adults are audiometry before treatment and during it, so that a switch to carboplatin or a dose change can be considered while hearing is still usable, and referral for hearing aids afterwards. In one adult cohort only 10 per cent of those with hearing loss used a hearing aid, and a third of those with hearing loss reported clinically significant functional impairment.
What comes back, and when: it does not. In a cohort assessed a median of 14 years after chemotherapy, 78 per cent had audiometrically defined hearing loss, and relative to age-matched norms hearing continued to deteriorate faster in those who had received more than 300 milligrams per square metre. OnCo found no study showing recovery of cisplatin hearing loss in adults. That is why prevention and early detection are the whole of the subject, and why hearing aids and assistive listening are part of survivorship care rather than an admission of defeat.
Cisplatin accumulates in the cochlea, where it is taken up by outer hair cells and the stria vascularis and is retained for years. Reactive oxygen species and apoptosis destroy outer hair cells from the basal, high-frequency end of the cochlea inward, and mammalian hair cells do not regenerate. Sodium thiosulfate is a thiol that inactivates circulating platinum; timing it six hours after the infusion is what separates protection of the ear from protection of the tumour.
Query for this technology: (TITLE:"Hearing and tinnitus after platinum chemotherapy" OR ABSTRACT:"Hearing and tinnitus after platinum chemotherapy") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Hearing and tinnitus after platinum chemotherapy, not a curated reading list.
Shares Testicular germ cell tumours, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Testicular germ cell tumours, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Testicular germ cell tumours, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Toxicity and quality of life are undervalued, Head and neck squamous cell carcinoma and the tags rejuvenation, survivorship.
Shares Testicular germ cell tumours, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected, Toxicity and quality of life are undervalued and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected, Toxicity and quality of life are undervalued and the tags rejuvenation, survivorship.
Shares Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected, Toxicity and quality of life are undervalued and the tags rejuvenation, survivorship.