van As Jorrit W, van den Berg Henk, van Dalen Elvira C
Princess Máxima Center for Pediatric Oncology, c/o Cochrane Childhood Cancer, Heidelberglaan 25, Utrecht, Netherlands, 3584 CS.
Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Department of Paediatric Oncology, PO Box 22660, Amsterdam, Netherlands, 1100 DD.
Cochrane Database Syst Rev. 2020 Jan 21;1(1):CD010885. doi: 10.1002/14651858.CD010885.pub5.
Platinum-based therapy, including cisplatin, carboplatin or oxaliplatin, or a combination of these, is used to treat a variety of paediatric malignancies. Unfortunately, one of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different platinum infusion durations have been studied. This review is the third update of a previously published Cochrane Review.
To assess the effects of different durations of platinum infusion to prevent hearing loss or tinnitus, or both, in children with cancer. Secondary objectives were to assess possible effects of these infusion durations on: a) anti-tumour efficacy of platinum-based therapy, b) adverse effects other than hearing loss or tinnitus, and c) quality of life.
We searched the electronic databases Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library 14 November 2019), MEDLINE (PubMed) (1945 to 14 November 2019) and Embase (Ovid) (1980 to 14 November 2019). In addition, we handsearched reference lists of relevant articles and we assessed the conference proceedings of the International Society for Paediatric Oncology (2009 up to and including 2019) and the American Society of Pediatric Hematology/Oncology (2014 up to and including 2019). We scanned ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP; apps.who.int/trialsearch) for ongoing trials (both searched on 4 November 2019).
Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing different platinum infusion durations in children with cancer. Only the platinum infusion duration could differ between the treatment groups.
Two review authors independently performed the study selection, 'Risk of bias' assessment and GRADE assessment of included studies, and data extraction including adverse effects. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
We identified one RCT and no CCTs; in this update no additional eligible studies were identified. The RCT (total number of children = 91) evaluated the use of a continuous cisplatin infusion (N = 43) versus a one-hour bolus cisplatin infusion (N = 48) in children with neuroblastoma. For the continuous infusion, cisplatin was administered on days one to five of the cycle, but it is unclear if the infusion duration was a total of five days. Risk of bias was present. Only results from shortly after induction therapy were provided. No clear evidence of a difference in hearing loss (defined as asymptomatic and symptomatic disease combined) between the different infusion durations was identified as results were imprecise (risk ratio (RR) 1.39, 95% confidence interval (CI) 0.47 to 4.13, low-quality evidence). Although the numbers of children were not provided, it was stated that tumour response was equivalent in both treatment arms. With regard to adverse effects other than ototoxicity, we were only able to assess toxic deaths. Again, the confidence interval of the estimated effect was too wide to exclude differences between the treatment groups (RR 1.12, 95% CI 0.07 to 17.31, low-quality evidence). No data were available for the other outcomes of interest (i.e. tinnitus, overall survival, event-free survival and quality of life) or for other (combinations of) infusion durations or other platinum analogues.
AUTHORS' CONCLUSIONS: Since only one eligible RCT evaluating the use of a continuous cisplatin infusion versus a one-hour bolus cisplatin infusion was found, and that had methodological limitations, no definitive conclusions can be made. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. For other (combinations of) infusion durations and other platinum analogues no eligible studies were identified. More high-quality research is needed.
铂类疗法，包括顺铂、卡铂或奥沙利铂，或这些药物的联合使用，用于治疗多种儿童恶性肿瘤。不幸的是，最重要的不良反应之一是听力丧失或耳毒性的发生。为了预防这种耳毒性，人们对不同的铂输注持续时间进行了研究。本综述是之前发表的Cochrane综述的第三次更新。
评估不同铂输注持续时间对预防癌症儿童听力丧失或耳鸣或两者的效果。次要目的是评估这些输注持续时间对以下方面的可能影响：a）铂类疗法的抗肿瘤疗效，b）除听力丧失或耳鸣之外的不良反应，以及c）生活质量。
我们检索了电子数据库Cochrane对照试验中心注册库（CENTRAL；Cochrane图书馆2019年11月14日）、MEDLINE（PubMed）（1945年至2019年11月14日）和Embase（Ovid）（1980年至2019年11月14日）。此外，我们手工检索了相关文章的参考文献列表，并评估了国际儿科肿瘤学会（2009年至2019年，包括2019年）和美国儿科血液学/肿瘤学会（2014年至2019年，包括2019年）的会议记录。我们在ClinicalTrials.gov和世界卫生组织国际临床试验注册平台（WHO ICTRP；apps.who.int/trialsearch）上搜索了正在进行的试验（两者均于2019年11月4日进行搜索）。
比较癌症儿童不同铂输注持续时间的随机对照试验（RCT）或对照临床试验（CCT）。仅治疗组之间的铂输注持续时间可以不同。
两位综述作者独立进行研究选择、纳入研究的“偏倚风险”评估和GRADE评估，以及包括不良反应在内的数据提取。分析按照Cochrane干预措施系统评价手册的指南进行。
我们确定了一项RCT，未发现CCT；在本次更新中未识别出其他符合条件的研究。该RCT（儿童总数=91）评估了神经母细胞瘤儿童连续输注顺铂（N=43）与一小时推注顺铂（N=48）的使用情况。对于连续输注，顺铂在周期的第1至5天给药，但不清楚输注持续时间是否总共为5天。存在偏倚风险。仅提供了诱导治疗后不久的结果。由于结果不精确（风险比（RR）1.39，95%置信区间（CI）0.47至4.13，低质量证据），未发现不同输注持续时间之间听力丧失（定义为无症状和有症状疾病合并）存在差异的明确证据。虽然未提供儿童数量，但指出两个治疗组的肿瘤反应相当。关于耳毒性以外的不良反应，我们仅能评估毒性死亡情况。同样，估计效应的置信区间太宽，无法排除治疗组之间的差异（RR 1.12，95%CI 0.07至17.31，低质量证据）。对于其他感兴趣的结局（即耳鸣、总生存期、无事件生存期和生活质量）或其他输注持续时间或其他铂类似物的组合，没有可用数据。
由于仅发现一项评估连续输注顺铂与一小时推注顺铂使用情况的符合条件的RCT，且该研究存在方法学局限性，因此无法得出明确结论。应注意的是，本综述中确定的“无效应证据”与“无效应证据”不同。对于其他输注持续时间（或组合）和其他铂类似物，未识别出符合条件的研究。需要更多高质量的研究。
