Ototoxicity Review: A Growing Number of Non–Platinum‐Based Chemo‐ and Immunotherapies

Abstract

Objective To raise awareness of the growing list of non–platinum-based chemo- and immunotherapeutic agents that have been associated with ototoxicity and to introduce the possible mechanism of ototoxicity of these agents. Data Sources PubMed, Embase, and Web of Science. Review Methods A systematic review was performed following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). PubMed, Embase, and Web of Science databases were searched for published reports of ototoxicity from non–platinum-based chemo- and immunotherapeutic agents in adult and pediatric patients. Therapies that utilized any platinum-based agent were excluded. Conclusions Ototoxicity from non–platinum-based chemo- and immunotherapies is an evolving problem. There were 54 reports—39 case reports and 15 cohort studies—documenting ototoxicity from 7 agents/combination therapies. Of these reports, 37 (69%) were published within the last 15 years (after 2005). No recovery of hearing was documented in 21 of 56 cases (38%). Pretreatment audiograms were uncommon (19/54 studies, 35%), despite documented ototoxic associations. Implications for Practice There is a growing number of novel, ototoxic, non–platinum-based chemo- and immunotherapeutic agents with various potential mechanisms of action. Otolaryngologists will need to prioritize awareness of these agents. This growing list of agents, many of which have reversible effects, suggest a need for standardized ototoxicity monitor protocols so that appropriate and timely management options can be implemented.

Potential Ototoxicity of Insulin-like Growth Factor 1 Receptor Signaling Inhibitors: An In Silico Drug Repurposing Study of the Regenerating Cochlear Neuron Transcriptome

“…Certain drugs are known to be ototoxic and to cause excitotoxic damage, functional impairment, and the degeneration of inner ear cells such as SGNs, including platinumbased chemotherapeutics, aminoglycoside antibiotics, loop diuretics, and non-steroidal anti-inflammatory drugs [6,18,19]. As the process of drug discovery advances, novel compounds and classes have been revealed to have ototoxic effects, such as some newer non-platinum-based chemo-and immunotherapies [18,20]. An example of a novel, potentially ototoxic drug class includes inhibitors of insulin-like growth factor 1 and its receptor (IGF-1/R) [21,22].…”

Sustained Cognitive Improvement in Patients over 65 Two Years after Cochlear Implantation

“…By the year 2050, it is expected that more than 2.5 billion people will have some degree of hearing loss, and 700 million will have severe hearing loss [1]. The causative factors contributing to hearing loss include, among others, occupational [2] or during-leisure [3] noise exposure, the use of ototoxic medications [4][5][6], mutations in genes essential for auditory function [7], compression of auditory tissues by tumors (vestibular schwannomas or meningiomas) [8,9], or the effects of cardiovascular diseases [10]. However, one of the most common causes of hearing loss is the aging process [11,12].…”