Introduction
Platinum chemotherapy agents are the cornerstone of several oncologic and hematologic protocol treatments given their high effectiveness, cost, and accessibility (Dillard et. al, 2022). These benefits are tied to unwanted side effects. Ototoxicity is a well-known adverse effect of platinum compounds, such as cisplatin and carboplatin, that may cause permanent hearing loss, tinnitus, or vestibular disturbances in 40–80% of treated adult patients, which is globally estimated to be half a million cases per year (Dillard et. al, 2022, Frisina et al., 2016). Ototoxicity type and degree vary depending on sex, age, genetic predisposition, changes in protein expressions, previous neuro-otological symptoms, chemotherapy interval of administration, dose regimen (up to 100% of patients have been found to be affected in a dose range between 150–225 mg/m2), concomitant radiotherapy treatments, or even the patient’s stress level (Kirkim et al., 2015, Charif et al., 2019, Coling et al., 2007, Bielefeld et al., 2021, Chan et al., 2018, Miaskowski et al., 2018). Current knowledge has shown platinum-induced ototoxicity is a multifactorial process where free radical oxygen species and inflammation induce endogenous antioxidants depletion and increase lipid peroxidation, causing rupture of the outer hair cell stereocilia in the organ of Corti (Gentilin et al, 2019, Tang et al., 2021). This process may have an acute or progressive onset, as cisplatin is retained in the cochlea indefinitely, activating the apoptotic pathway in the marginal cells on the stria vascularis region that maintains the endolymph composition (Breglio et al., 2017). Depending on the hearing loss frequency and the severity of speech impairment, more than ten grading systems have been proposed to better characterize patients´ affection(Waissbluth et al., 2017). Moreover, accurate prediction models of posttreatment hearing alterations with good performance (eg. sensitivity of 80% and specificity of 75%) and follow-up screening audiometric test analysis have been proposed to diagnose platinum ototoxicity (Shuette et al., 2020, Frisina et al., 2016, Ardeshirrouhanifard et al., 2022). However, there is a paucity of safe and effective pharmacological or non-pharmacological options to prevent or treat platinum-induced ototoxicity in adults, without inhibiting antitumor effects. Numerous studies on animals have been conducted with relative success and a guideline to treat cisplatin-induced ototoxicity in children has been published (Freyer et al., 2020), albeit the evidence concerning the adult population is sparse, non-pharmacologic treatments have not been systematically researched, and the use of otoprotecting strategies for other chemotherapy agents besides platinums is anecdotal (Desilets et al., 2020). Even so, ototoxicity prevention and treatment is a major research priority due to the symptom burden and diminishing quality of life patients experience (Miaskowski et al., 2018). Thus, we conducted a comprehensive systematic literature review on pharmacological or non-pharmacological interventions to prevent or treat platinum-induced ototoxicity in adult cancer patients.