依托泊苷/达卡巴嗪进入WHO儿童药物基本目录治疗儿童霍奇金淋巴瘤有效性、安全性和经济性的循证快速评估

中图分类号 R95 文献标志码 A 文章编号 1001-0408（2018）19-2593-05

DOI 10.6039/j.issn.1001-0408.2018.19.01

摘 要 目的：按世界卫生组织（WHO）儿童基本药物目录（EMLc）专家委员会要求，循证快速评估依托泊苷/达卡巴嗪治疗儿童霍奇金淋巴瘤的有效性、安全性和经济性，为其是否纳入第5版WHO EMLc提供证据。方法：系统检索Cochrane图书馆、PubMed、Embase、WHO国际临床试验注册平台（ICTRP）、美国国家指南（NGC）数据库和Google学术搜索，检索时限均为建库起至2015年1月。获取依托泊苷/达卡巴嗪治疗儿童霍奇金淋巴瘤有效性、安全性和经济性的临床研究、指南和系统评价，分别采用AMSTAR、Cochrane handbook和ACROBAT-NRSI工具评估系统评价/Meta分析、随机对照试验（RCT）和观察性研究的文献质量，采用GRADE标准（2011）评价证据质量和推荐强度。结果：最终纳入8篇文献。有效性方面，1篇循证指南推荐使用依托泊苷治疗儿童霍奇金淋巴瘤；5项RCT中，2項含依托泊苷/达卡巴嗪方案的无进展生存率（EFS）和总体生存率（OS）均在75%以上，但2项含达卡巴嗪方案的EFS、OS和1项含依托泊苷方案的完全缓解率（CR）与其他化疗方案比较，差异均无统计学意义；安全性方面，含依托泊苷/达卡巴嗪方案的不良事件主要包括中性粒细胞减少、骨髓抑制、肺毒性、恶心呕吐及二次恶性肿瘤，但均可耐受。经济性方面，ABVD方案在发达国家可负担，在发展中国家较昂贵。GRADE结果显示证据质量为中等。结论：推荐依托泊苷/达卡巴嗪作为儿童霍奇金淋巴瘤的治疗药物纳入第5版WHO儿童基本药物清单中。

关键词 依托泊苷；达卡巴嗪；儿童霍奇金淋巴瘤；儿童基本药物目录

ABSTRACT OBJECTIVE： To evaluate efficacy， safety and econimics of etoposide/dacarbazine for pediatric Hodgkin lymphoma according to the requirements of WHO pediatric EMLc Expert Committee， and to provide the evidence whether etoposide and dacarbazine should be included in fifth edition of WHO EMLc. METHODS： Retrieved from the Cochrane Library， PubMed， Embase， WHO ICTRP， NGC database and Google scholar search systematically， clinical studies， guideline and systematic review about efficacy， safety and safety of etoposide/dacarbazine for pediatric Hodgkin lymphoma were collected from database establishment to Jan. 2015. The quality of systematic evaluation/Meta-analysis， RCT and observational research literature were evaluated by using AMSTAR， Cochrane handbook and ACROBAT-NRSI tool. The quality of evidence and recommended intensity were evaluated by using GRADE （2011）. RESULTS： Totally 8 literatures were included. For efficacy： one evidence-based guideline supported the use of etoposide for the treatment of pediatric Hodgkin lymphoma. Among 5 RCTs， progression-free survival （EFS） and overall survival （OS） of 2 schemes containing etoposide/dacarbazine were all higher than 75%， but there was no statistical significance in EFS and OS of 2 schemes containing dacarbazine， complete remission （CR） of 1 scheme containing etoposide， compared with other chemotherapy plan. For safety， adverse events of schemes containing etoposide/dacarbazine containing mainly included neutrophils， bone marrow suppression， lung toxicity， nausea and vomiting， and secondary malignant tumors， which were all tolerable. For economics， ABVD regimen was affordable for developed countries， but expensive for developing countries. GRADE results showed that evidence had moderate quality. CONCLUSIONS： It is recommended to include etoposide/dacarbazine for treatment of pediatric Hodgkin lymphoma into fifth edition of WHO pediatric EMLc.