Mechanisms of cisplatin ototoxicity and progress in otoprotection.
OBJECTIVE
This review presents exciting new data published in the past year that help to elucidate the mechanisms of cisplatin ototoxicity. Recent research findings on otoprotection could lead to the development of novel protective agents. Cisplatin ototoxicity is a frequent and serious problem in patients. Strategies to ameliorate ototoxicity without interfering with the desired therapeutic effects are urgently needed.


RESULTS
Cisplatin ototoxicity appears to involve the production of reactive oxygen species in target tissues in the inner ear by activating an enzyme unique to the cochlea. This leads to a cascade resulting in oxidation of lipids and cell death. The upregulation of endogenous protective mechanisms in the cochlea or treatment with exogenous compounds reduces ototoxicity in cisplatin-treated animals. The only clinical trials reported to date with the putative protective agent, amifostine, have been disappointing.


CONCLUSIONS
The data summarized in this paper could lead to important clinical trials to determine whether the findings in experimental animals can translate into effective treatments to prevent cisplatin ototoxicity.
Rybak
Leonard P
LP
Division of Otolaryngology, Department of Surgery, Southern Illinois University, School of Medicine, Springfield, Illinois 62794-9653, USA. lrybak@siumed.edu
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D012307:Risk Factors