Xiao Zheng, Wang Chengqiong, Tan Zhouke, Hu Shanshan, Chen Yali, Zhou Minghua, Feng Jihong, Liu Shiyu, Chen Ling, Ding Jie, Gong Qihai, Tang Fushan, Liu Hui, Li Xiaofei
Evidence-Based Medicine Center, MOE Virtual Research Center of Evidence-based Medicine at Zunyi Medical College, Affiliated Hospital of Zunyi Medical College, Zunyi, China.
Department of Respiratory Medicine (Center for Evidence-Based and Translational Medicine of major infectious diseases), Affiliated Hospital of Zunyi Medical College, Zunyi, China.
J Clin Pharm Ther. 2019 Feb;44(1):23-38. doi: 10.1111/jcpt.12761. Epub 2018 Sep 19.
Sodium cantharidinate has been widely used in lung cancer treatment in China. To investigate whether sodium cantharidinate improves clinical effectiveness in non-small-cell lung cancer, we systematically re-evaluated all related studies.
All studies of cantharidinate for non-small-cell lung cancers (NSCLC) were selected from the MEDLINE, EMBASE, Web of Science (ISI), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), WHO International Clinical Trials Registry Platform (WHO-ICTRP) and US-clinical trials databases (established to September 2017). Their quality was evaluated using the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0). The data were extracted following PICO principles and synthesized through meta-analysis.
We included 38 trials involving 2845 patients, but most trials had an unclear risk of bias. Sodium cantharidinate could increase the objective response rate (ORR) (1.52, (1.40-1.66]), disease control rate (DCR) (1.20, [1.16-1.25]) and quality of life (QOL) (1.76, [1.56-1.98]), but not the 1-year overall survival (OS) rate (1.16, [0.91-1.47]) and the 2-year OS rate (1.21, [0.51-2.91]). Subgroup analysis revealed that sodium cantharidinate and vitamin B6 at 0.5, 0.4 or 0.3 mg, and cantharidinate at 0.5 mg could all increase the ORR and DCR. Cantharidinate therapy had a lower risk of neutropenia (0.58, [0.50-0.67]), thrombocytopenia (0.57, [0.45-0.72]), gastrointestinal reaction (0.65, [0.52-0.82]) and nausea/vomiting (0.56, [0.41-0.76]) than that of chemotherapy alone. Sensitivity analysis showed that the results had good robustness.
Current evidence reveals that sodium cantharidinate can improve tumour responses and QOL with a lower risk of haematotoxicity and gastrointestinal toxicity than chemotherapy alone in NSCLC. However, the evidence does not indicate that it can improve long-term survival rates.
斑蝥酸钠在中国已广泛应用于肺癌治疗。为探究斑蝥酸钠是否能提高非小细胞肺癌的临床疗效，我们对所有相关研究进行了系统的重新评估。
从MEDLINE、EMBASE、科学引文索引（ISI）、中国知网数据库（CNKI）、维普中文科技期刊全文数据库（VIP）、万方数据库、中国生物医学文献数据库（CBM）、Cochrane系统评价数据库（CENTRAL）、中国临床试验注册中心（Chi-CTR）、世界卫生组织国际临床试验注册平台（WHO-ICTRP）以及美国临床试验数据库（截至2017年9月）中筛选出所有关于斑蝥酸钠治疗非小细胞肺癌（NSCLC）的研究。采用Cochrane随机对照试验（RCT）评价手册（5.1.0版）对其质量进行评估。按照PICO原则提取数据，并通过荟萃分析进行综合。
我们纳入了38项试验，涉及2845例患者，但大多数试验的偏倚风险不明确。斑蝥酸钠可提高客观缓解率（ORR）（1.52，[1.40 - 1.66]）、疾病控制率（DCR）（1.20，[1.16 - 1.25]）和生活质量（QOL）（1.76，[1.56 - 1.98]），但不能提高1年总生存率（OS）（1.16，[0.91 - 1.47]）和2年总生存率（1.21，[0.51 - 2.91]）。亚组分析显示，斑蝥酸钠与0.5、0.4或0.3 mg的维生素B6联合使用，以及0.5 mg的斑蝥酸钠单独使用，均可提高ORR和DCR。与单纯化疗相比，斑蝥酸钠治疗导致中性粒细胞减少（0.58，[0.50 - 0.67]）、血小板减少（0.57，[0.45 - 0.72]）、胃肠道反应（0.65，[0.52 - 0.82]）和恶心/呕吐（0.56，[0.41 - 0.76]）的风险更低。敏感性分析表明结果具有良好的稳健性。
目前的证据表明，在非小细胞肺癌中，斑蝥酸钠可改善肿瘤反应和生活质量，且与单纯化疗相比，血液毒性和胃肠道毒性风险更低。然而，现有证据并未表明其能提高长期生存率。
