硫代硫酸钠和观察对发展的影响cisplatin-induced听力损失儿童癌症(ACCL0431):一个多中心、随机、对照、开放第三阶段试验。

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福瑞尔博士,陈L, Krailo MD,骑士K, Villaluna D,幸福B,波洛克BH, Ramdas J,兰格B,范·霍夫D, VanSoelen ML, Wiernikowski J, Neuwelt EA,唱L

硫代硫酸钠和观察对发展的影响cisplatin-induced听力损失儿童癌症(ACCL0431):一个多中心、随机、对照、开放第三阶段试验。

柳叶刀杂志。2017年1月,18 (1):63 - 74。doi: 10.1016 / s1470 - 2045 (16) 30625 - 8。Epub 2016 12月1。

PubMed ID
27914822 (在PubMed
]
文摘

背景:硫代硫酸钠是一种抗氧化剂在临床前研究表明动物防止cisplatin-induced听力损失与时间政府顺铂后在不影响顺铂抗肿瘤功效。本研究的主要目的是评估硫代硫酸钠cisplatin-induced听力损失的预防儿童和青少年。方法:ACCL0431是一个多中心、随机、非盲、第三阶段试验注册参加38参与儿童肿瘤协会医院在美国和加拿大。合格的参与者队岁与新诊断癌症和正常听力测定被随机分配接受硫代硫酸钠(1:1)或观察(对照组)除了他们的计划cisplatin-containing化疗方案,使用排列的四块。随机最初分层注入顺铂的年龄和持续时间。前颅辐照是后来添加的分层的协议修正案。分配序列生成的集中和隐藏所有人员。参与者收到了硫代硫酸钠16 g / m(2)静脉注射后6 h每个剂量顺铂或观察。听力损失的主要终点是发病率4周后最终顺铂剂量。听力测定使用标准的听力测定和审查由听力学家蒙面集中分配使用美国演讲语言听力协会标准但不戴面具的参与者或临床医生治疗。 Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. FINDINGS: Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28.6%; 95% CI 16.6-43.3) participants in the sodium thiosulfate group compared with 31 (56.4%; 42.3-69.7) in the control group (p=0.00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0.31, 95% CI 0.13-0.73; p=0.0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. INTERPRETATION: Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. FUNDING: US National Cancer Institute.

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