Cisplatin-Induced Ototoxicity: Mechanisms and Pharmacological Interventions

Cisplatin is a metal-based chemotherapeutic agent frequently used for various solid tumors, including testicular, ovarian, bladder, lung, cervical, gastric, and head and neck cancers. Unfortunately, cisplatin use can be limited due to its side effects, as it can cause multiple systemic toxicities, including ototoxicity. Cisplatin-induced ototoxicity (CIO) affects about 40-70% of adult patients; hearing loss induced by cisplatin is permanent, leading to a devastating effect on patients’ quality of life. This review article provides an overview of the mechanisms of CIO, primarily oxidative stress, inflammation, and apoptosis of cochlear cells following cisplatin therapy, and evaluates otoprotective agents using preclinical and clinical evidence. Sodium thiosulfate (STS) exhibits an otoprotective effect, based on evidence from human data (phase 3 randomized-controlled trials (RCTs), FDA-approved for pediatrics). Other agents, including D-methionine, Vitamin E, and statins, are promising but require further research via RCTs with large sample sizes.