Ototoxicity of chemotherapeutic agents

This chapter summarizes the reported ototoxicity data on the most clinically important ototoxic chemotherapeutic agents, notably emphasizing the oto(neuro)toxicities of the more commonly administered platinum compounds, cisplatin and carboplatin. Currently, in the United States, the only other marketed ototoxic chemotherapeutic agents are nitrogen mustard, alpha-difluoromethyl ornithine (DFMO), and the vinca alkaloids (vincristine and vinblastine sulfate); for these groups, animal ototoxicity data is sparse, and audiovestibular records of human ototoxicity are not available from most prospective, randomized controlled clinical trials. Future phase I, II, and III clinical oncologic trials of "experimental" chemotherapeutic agents should include methodology for audiovestibular monitoring, just as present FDA-approved cancer protocols with either monotherapy or combined therapy of known "ototoxic" agents should include standardized audiovestibular assessment in the database. Finally, continued clinical application of cisplatin alone or in combination with other chemotherapeutic agents in the successful treatment of solid tumors mandates decreasing or eliminating specifically the dose-dependent sensorineural hearing loss (partially in cases of complete or long-term partial remission) in addition to other common antiproliferation-induced side effects (nephritis, peripheral neuropathy, intractable nausea and vomiting, electrolyte imbalance, anaphylactic-like reactions, and myelosuppression). Because of the chemotherapeutic superiority of cisplatin, it is essential to continue to investigate methods of altering the dose-limiting oto(neuro)toxicity without causing a "counterproductive" reduction of the antitumor activity of cisplatin (or other second- or third-generation ototoxic platinum agents).