Pharmacological otoprotection strategies against cisplatin-induced ototoxicity

Cisplatin is a platinum-based chemotherapeutic agent, known to be one of the most active platinum compounds in cancer treatment. It is highly effective in the treatment of soft-tissue neoplasms, lung cancer, squamous cell cancer, cancer of the head and neck, testicular, ovarian, cervical, and bladder cancer. Ototoxicity is an important and dose-limited side-effect of cisplatin therapy apart from nephrotoxicity and neurotoxicity. This is mainly due to the generated reactive oxygen species (ROS). In ototoxicity the ROS have a significant effect on the outer hair cells (OHCs) in the organ of Corti. Many agents with chemoprotective action against cisplatin-induced ototoxicity have been tested for a long time. Some show promising results in animal models, but it is important to verify these promising results in future clinical trials. The possible administration modalities of an otoprotector are systemic and transtympanic (local). Considering the technical difficulties and the physical and mental status of a patient undergoing treatment for neoplasms, systemic administration seems to stand ahead of local administration. When using a chemoprotective agent systemically it is important that the compound will not affect the anti-tumour effect of cisplatin. Promising results of an otoprotector in clinical practice will let us increase the dose of cisplatin in treatment which will increase the effectiveness of cisplatin therapy and so improve the quality of life for a large group of patients.