Cisplatin-Induced Ototoxicity: Effects, Mechanisms and Protection Strategies

Abstract

Cisplatin is a highly effective chemotherapeutic agent that is widely used to treat solid organ malignancies. However, serious side effects have been associated with its use, such as bilateral, progressive, irreversible, dose-dependent neurosensory hearing loss. Current evidence indicates that cisplatin triggers the production of reactive oxygen species in target tissues in the inner ear. A variety of agents that protect against cisplatin-induced ototoxicity have been successfully tested in cell culture and animal models. However, many of them interfere with the therapeutic effect of cisplatin, and therefore are not suitable for systemic administration in clinical practice. Consequently, local administration strategies, namely intratympanic administration, have been developed to achieve otoprotection, without reducing the antitumoral effect of cisplatin. While a considerable amount of pre-clinical information is available, clinical data on treatments to prevent cisplatin ototoxicity are only just beginning to appear. This review summarizes clinical and experimental studies of cisplatin ototoxicity, and focuses on understanding its toxicity mechanisms, clinical repercussions and prevention strategies.

Early ototoxic changes in patients with germ cell tumor after first cycle of cisplatin‐based therapy

“…Any individual marker would be beneficial for clinicians to adapt protection strategies in case of affected patients. Protection strategies, including locally or systematically administered drugs or other agents, and the molecular mechanisms of cisplatin‐induced ototoxicity such as the role of antioxidants, were described in detail in some relevant reviews . A better selection of patients who do not require adjuvant cisplatin‐based therapy in stage I germ cell testicular cancer is very important.…”

Genetic and Modifiable Risk Factors Contributing to Cisplatin-induced Toxicities

“…Although not the focus of this review, mechanisms by which cisplatin elicits these toxicities are listed in Table 1. For a more comprehensive description, refer to previous reviews for ototoxicity (4)(5)(6)(7), neurotoxicity (8,9), nephrotoxicity (10)(11)(12), myelosuppression (13), and nausea/emesis (14,15).…”

Phase 1 study to evaluate safety, tolerability and pharmacokinetics of a novel intra-tympanic administered thiosulfate to prevent cisplatin-induced hearing loss in cancer patients

“…Serious side effects of cisplatin treatment include neurotoxicity, nephrotoxicity and ototoxicity often leading to permanent hearing loss. To date, no approved therapy to prevent or treat ototoxicity exists for patients receiving cisplatin treatment, which remains a major dose-limiting side effect of cisplatin administration [2].…”