儿童及青少年患者靶向抗肿瘤药皮肤不良反应的系统评价

Dermatologic Adverse Events Related to Targeted Anti-cancer Agents in Children and Teenager: A Systematic Review

目的:系统评价儿童及青少年患者应用靶向抗肿瘤药的皮肤不良反应,为后续研究及临床实践提供参考。方法:检索Pub Med(http:∥www.ncbi.nlm.nih.gov/pubmed/)、美国临床肿瘤学会年会摘要集(http:∥www.asco.org/)与Clinical Trials.gov(http:∥www.clinicaltrials.gov)以获取涉及靶向药物(单药或多种靶向药物联合治疗)用于儿童及青少年患者,并有皮肤不良反应报告的临床试验。对入选研究进行质量评价(非随机对照试验用MINORS量表,随机对照试验用Cochrane偏倚风险评价工具),并提取资料。以各类皮肤不良反应(皮疹、皮肤干燥、瘙痒与黏膜炎)发生率为结局指标进行Meta分析。结果:共纳入24项研究,涉及960名患者。研究疾病涉及多种实体瘤与白血病。共涉及14种不同的靶向抗肿瘤药。绝大多数研究为高质量研究。Meta分析结果显示,皮疹的合并事件率及其95%置信区间(CI)为0.19[0.12~0.28],皮肤干燥为0.24[0.06~0.51],瘙痒为0.12[0.04~0.24]以及黏膜炎为0.21[0.07~0.39]。发表偏倚分析提示皮疹之结局指标的报道可能存在发表偏倚(Egger’s P=0.007)。结论:靶向抗肿瘤药应用于儿童或青少年人群可引起部分患者出现皮疹、皮肤干燥等不良反应。这些不良反应影响生活质量并可能导致残疾,临床应用时需予重视。

s Database（ http//www, asco. org/） and Clini-calTrials, gov（http：//www, clinicaltrials, gov） were searched for the clinical trials on the use of targeted anti-cancer drugs （ single orcombination） in children and teenager complicated with dermatologic toxicity. Methodological quality assessment was performed for theincluded studies, using Cochrane＇ s risk of bias assessment tool for randomized controlled trials and methodological index for non-ran-domized studies （MINORS）. Meta-analysis was performed for the outcomes including adverse event rate of skin rash, xerosis, pruritisand mucositis. Results： A total of 24 studies with 960 patients were included in this study. Various solid tumors and leukemia were in-vestigated in the studies. The quality assessment revealed that the majority of included studies were with high quality. According to theresults of meta-analysis, the pooled event rate and 95% confidence interval were 0.19 [ 0.12-0.28 ] ,0.24 [ 0.06-0.51 ] ,0. I2 [ 0.04-0.24] and 0.21 [0.07-0.39] for skin rash, xerosis, pruritis and mucositis, respectively. Publication bias analysis indicated potentialreporting bias for skin rash （Egger＇ s P =0.007 ）. Conclusion： Dermatotogic adverse events occur in a part of children and teenagerwith cancer treated with targeted therapy, which may cause impaired quality of life and disability. Adequate attention should be paid tothese events during clinical trials and real life practice.