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

Expert Opin Drug Metab Toxicol. 2020 Oct;16(10):965-982. doi: 10.1080/17425255.2020.1806235. Epub 2020 Sep 29.

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. The mechanisms of cochlear damage are still being investigated. However, it appears that inner ear damage is triggered by reactive oxygen species (ROS) formation and inflammation 34.

Areas covered: 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 ROS and reactive nitrogen species, and blocking pathways that produce inflammation, including TRPV1 and STAT1 36.

Expert opinion: Numerous potential protective agents show promise in animal models by systemic or local administration. However, clinical trials have not shown much efficacy to date with the exception of sodium thiosulfate. 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 151.

Keywords: Cisplatin; clinical trials; cochlea; drug targets; hearing loss; mechanisms; ototoxicity; transtympanic.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Child
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Hearing Loss / chemically induced
  • Hearing Loss / prevention & control
  • Humans
  • Neoplasms / drug therapy
  • Ototoxicity / etiology
  • Ototoxicity / prevention & control*
  • Platinum Compounds / administration & dosage
  • Platinum Compounds / adverse effects*
  • Protective Agents / administration & dosage
  • Protective Agents / adverse effects
  • Protective Agents / pharmacology
  • Quality of Life
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Platinum Compounds
  • Protective Agents
  • Reactive Oxygen Species
  • Cisplatin