Strategies to reduce the risk of platinum containing antineoplastic drug-induced ototoxicity

Abstract

Introduction-Cisplatin is a highly effective chemotherapeutic agent against a variety of solid tumors in adults and in children. Unfortunately, a large percentage of patients suffer permanent sensorineural hearing loss. Up to 60% of children and at least 50% of adults suffer this complication that seriously compromises their quality of life. Hearing loss is due to damage to the sensory cells in the inner ear, primarily the outer hair cells and cells of the stria vascularis and spiral ganglion. The mechanisms of cochlear damage are still being investigated. However, it appears that most damage to the inner ear is triggered by reactive oxygen species (ROS) formation and inflammation.Areas covered-In this review we discuss a number of potential therapeutic targets that can be addressed to provide hearing protection. These strategies include enhancing the endogenous antioxidant pathways, heat shock proteins, G protein coupled receptors and counteracting enzymes that produce ROS and reactive nitrogen species, and blocking pathways that produce inflammation, including TRPV1 and STAT1.Expert opinion-A number of potential protective agents show promise in animal models by systemic or local administration by transtympanic or intracochlear injection. However, clinical trials have not shown much efficacy to date with the exception of sodium thiosulfate administration in two studies of pediatric tumors. There is an urgent need to discover safe and effective protective agents that do not interfere with the efficacy of cisplatin against tumors yet preserve hearing.

Ruthenium Half-Sandwich Type Complexes with Bidentate Monosaccharide Ligands Show Antineoplastic Activity in Ovarian Cancer Cell Models through Reactive Oxygen Species Production

“…Metal-based drugs used in cancer therapy include square planar platinum(II) complexes, e.g., cisplatin ( Figure 1 , I ), oxaliplatin ( II ), and carboplatin ( III ), which are registered worldwide. Although Pt complexes are versatile tools of the trade, their applicability has shortcomings, such as the development of platinum resistance in tumors [ 1 , 2 ], ototoxicity [ 3 ], and nephrotoxicity [ 4 , 5 ], with the latter two being very characteristic for cisplatin.…”

Preferential Cochleotoxicity of Cisplatin

“…Unlike other side effects of cisplatin (such as nephrotoxicity), ototoxicity can cause irreversible injury to the inner ear as human inner ear sensory hair cells generally cannot regenerate ( Rubel et al, 2013 ). Furthermore, no known effective protective or curative strategies are presently available for cisplatin-induced ototoxicity although clinical trial data is emerging ( Mukherjea et al, 2020 ).…”

Evaluation of the Effect of Mesenchymal Stem Cells on Chemotherapy Response for Neuroblastoma Treatment in an Experimental Animal Model

“…Sensorineural hearing loss caused by CDDP of 60% in the childhood period and 50% in adults disrupts quality of life. As a result, development studies for potential protective agents are currently in progress [25]. However, apart from the use of sodium thiosulfate in childhood cancers, there is no agent with proven reliability and benefit at the level of clinical studies.…”