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Indexed/Abstracted in: EMBASE, Scopus
Online ISSN 1827-188X
INTRATYMPANIC THERAPIES FOR INNER EAR DISORDERS
Division of Otolaryngology, Department of Surgery, University of Connecticut Health Center, Farmington, CT, USA
Cisplatin-induced ototoxicity is a common side effect of chemotherapeutic regimens aimed at treating several types of malignant solid tumors. Cisplatin ototoxicity is likely mediated by multiple cellular mechanisms which lead to accumulation of reactive oxygen species (ROS) and apoptosis. Cisplatin targets in the cochlea include the outer hair cells (OHC), spiral ganglion cells and stria vascularis. There are currently a number of clinical trials underway to assess the efficacy of systemic antioxidants in ameliorating ototoxic side effects of cisplatin. However, there is concern that systemic administration of antioxidants may interfere with anti-neoplastic properties of chemotherapeutic regimens. Intratympanic (IT) administration of drugs offer an alternative route of delivery of ‘rescue’ medications to the cochlea to minimize systemic absorption, thus reducing the risk of altering the efficacy of chemotherapeutic regimens. This article reviews the available experimental evidence on the effectiveness of IT therapy in protecting auditory function from cisplatin ototoxicity. Promising agents include dexamethasone, which is currently in use in treatment of other diseases of the inner ear. Latest research has improved our understanding of the cellular mechanisms that lead to ototoxicity and permitted emergence of targeted therapeutic strategies, such as IT application of short interfering RNA to inhibit NADPH oxidase, a key generator of ROS. The experimental results reviewed in this paper suggest a promising future in protecting hearing against cisplatin-induced ototoxicity.