Platinum-Induced Ototoxicity in Children: A Consensus Review on Mechanisms, Predisposition, and Protection, Including a New International Society of Pediatric Oncology Boston Ototoxicity Scale
Platinum-Induced Ototoxicity in Children: A Consensus Review on Mechanisms, Predisposition, and Protection, Including a New International Society of Pediatric Oncology Boston Ototoxicity Scale
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DOI：
10.1200/jco.2011.39.1110
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发表时间：
2012-07-01
影响因子：
45.3
通讯作者：
Neuwelt, Edward A.
中科院分区：
文献类型：
--
作者：
Brock, Penelope R.;Knight, Kristin R.;Neuwelt, Edward A.
目的铂类化疗药物顺铂和卡铂广泛应用于成人和儿童肿瘤的治疗。顺铂导致至少60%的儿科患者听力丧失。降低顺铂和大剂量卡铂耳毒性而不降低疗效是重要的。患者和方法本综述总结了2010年10月21-24日在波士顿举行的第42届国际儿科肿瘤学会（SIOP）大会上提出的建议，反映了国际基础科学家、儿科肿瘤学家、耳鼻喉科医生、肿瘤学护士、听力学家和神经外科医生对发展和推进耳保护研究和临床试验的投入。结果铂最初对高频听力有损害，随着累积剂量的增加向低频发展。参与药物转运、代谢和DNA修复的基因调控铂的毒性。耳保护可以通过作用于这些途径来实现，通常涉及抗氧化剂硫醇剂。耳保护是一种正在探索的策略，在维持剂量强度或允许剂量增加的同时减少听力损失，但它有可能干扰杀肿瘤作用。给药途径和最佳时机相对于铂治疗是关键问题。此外，分级和比较耳毒性的国际标准对于旨在减少铂致听力损失的前瞻性儿科试验的成功至关重要。结论降低不可逆铂性听力损失发生率，优化癌症控制，需要开展前瞻性基础和临床试验协同研究。在当前和未来的耳保护试验中广泛使用新的国际商定的SIOP波士顿耳毒性量表将有助于实现这一目标。
PurposeThe platinum chemotherapy agents cisplatin and carboplatin are widely used in the treatment of adult and pediatric cancers. Cisplatin causes hearing loss in at least 60% of pediatric patients. Reducing cisplatin and high-dose carboplatin ototoxicity without reducing efficacy is important.Patients and MethodsThis review summarizes recommendations made at the 42nd Congress of the International Society of Pediatric Oncology (SIOP) in Boston, October 21-24, 2010, reflecting input from international basic scientists, pediatric oncologists, otolaryngologists, oncology nurses, audiologists, and neurosurgeons to develop and advance research and clinical trials for otoprotection.ResultsPlatinum initially impairs hearing in the high frequencies and progresses to lower frequencies with increasing cumulative dose. Genes involved in drug transport, metabolism, and DNA repair regulate platinum toxicities. Otoprotection can be achieved by acting on several these pathways and generally involves antioxidant thiol agents. Otoprotection is a strategy being explored to decrease hearing loss while maintaining dose intensity or allowing dose escalation, but it has the potential to interfere with tumoricidal effects. Route of administration and optimal timing relative to platinum therapy are critical issues. In addition, international standards for grading and comparing ototoxicity are essential to the success of prospective pediatric trials aimed at reducing platinum-induced hearing loss.ConclusionCollaborative prospective basic and clinical trial research is needed to reduce the incidence of irreversible platinum-induced hearing loss, and optimize cancer control. Wide use of the new internationally agreed-on SIOP Boston ototoxicity scale in current and future otoprotection trials should help facilitate this goal.