Hearing loss during chemotherapy: prevalence, mechanisms, and protection

Ototoxicity is an often-underestimated sequela for cancer patients undergoing chemotherapy, with an incidence rate exceeding 50%, affecting approximately 4 million individuals worldwide each year. Despite the nearly 2,000 publications on chemotherapy-related ototoxicity in the past decade, the understanding of its prevalence, mechanisms, and preventative or therapeutic measures remains ambiguous and subject to debate. To date, only one drug, sodium thiosulfate, has gained FDA approval for treating ototoxicity in chemotherapy. However, its utilization is restricted. This review aims to offer clinicians and researchers a comprehensive perspective by thoroughly and carefully reviewing available data and current evidence. Chemotherapy-induced ototoxicity is characterized by four primary symptoms: hearing loss, tinnitus, vertigo, and dizziness, originating from both auditory and vestibular systems. Hearing loss is the predominant symptom. Amongst over 700 chemotherapeutic agents documented in various databases, only seven are reported to induce hearing loss. While the molecular mechanisms of the hearing loss caused by the two platinum-based drugs are extensively explored, the pathways behind the action of the other five drugs are primarily speculative, rooted in their therapeutic properties and side effects. Cisplatin attracts the majority of attention among these drugs, encompassing around two-thirds of the literature regarding ototoxicity in chemotherapy. Cisplatin ototoxicity chiefly manifests through the loss of outer hair cells, possibly resulting from damages directly by cisplatin uptake or secondary effects on the stria vascularis. Both direct and indirect influences contribute to cisplatin ototoxicity, while it is still debated which path is dominant or where the primary target of cisplatin is located. Candidates for hearing protection against cisplatin ototoxicity are also discussed, with novel strategies and methods showing promise on the horizon.