Overview of cisplatin-induced neurotoxicity and ototoxicity, and the protective agents

Cisplatin has dramatically improved the survival rate of cancer patients, but it has also increased the prevalence of hearing and neurological deficits in this population. Cisplatin induces ototoxicity, peripheral (most prevalent) and central (rare) neurotoxicity. This review addresses the ototoxicity and the neurotoxicity associated with cisplatin-based chemotherapy, providing an integrated view of the potential protective agents that have been evaluated in vitro, in vivo and in clinical trials, their targets and mechanisms of protection and their effects on the antitumor activity of cisplatin. So far, the findings are insufficient to support the use of any oto- or neuroprotective agent before, during or after cisplatin chemotherapy. Despite their promising effects in vitro and in animal studies, many agents have not been evaluated in clinical trials. Additionally, the clinical trials have limitations concerning the sample size, controls, measurement, heterogeneous groups, several arms of treatment, short follow-up or no blinding. Besides that, for most agents, the effects on the antitumor activity of cisplatin have not been evaluated in tumor-bearing animals, which discourages clinical trials. Further well-designed randomized controlled clinical trials are necessary to definitely demonstrate the effectiveness of the oto- or neuroprotective agents proposed by animal and in vitro studies.