Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Food Chem Toxicol. 2020 Feb;136:111079. doi: 10.1016/j.fct.2019.111079. Epub 2019 Dec 28.
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.
顺铂显著提高了癌症患者的生存率，但也增加了该人群听力和神经缺陷的发生率。顺铂可引起耳毒性、外周（最常见）和中枢（罕见）神经毒性。本综述探讨了与顺铂为基础的化疗相关的耳毒性和神经毒性，提供了已在体外、体内和临床试验中评估的潜在保护剂的综合视图，以及它们的作用靶点、保护机制及其对顺铂抗肿瘤活性的影响。到目前为止，这些发现还不足以支持在顺铂化疗前、期间或之后使用任何耳或神经保护剂。尽管它们在体外和动物研究中具有很大的潜力，但许多药物尚未在临床试验中进行评估。此外，临床试验在样本量、对照、测量、异质组、多个治疗臂、随访时间短或无盲法方面存在局限性。除此之外，对于大多数药物，在荷瘤动物中尚未评估其对顺铂抗肿瘤活性的影响，这阻碍了临床试验的开展。需要进一步设计良好的随机对照临床试验，以明确证实动物和体外研究中提出的耳或神经保护剂的有效性。
