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.