Zhang Yingshi, Hui Fuhai, Yang Yue, Chu Haixiao, Qin Xiaochun, Zhao Mingyi, Zhao Qingchun
Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China.
Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, P.R. China.
Oncotarget. 2017 Sep 15;8(63):107258-107272. doi: 10.18632/oncotarget.20921. eCollection 2017 Dec 5.
To assess the comparative efficacy and safety of combination treatment with Compound Kushen Injection (CKI) and transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and to identify the best conditions for using CKI.
We performed a network meta-analysis based on randomized controlled trials. We searched databases for studies published by August 2017. The prespecified primary efficacy outcome was treatment response, while the secondary efficacy outcomes were KPS score, Child-Pugh score, overall survival rate, clinical symptoms, and improvements in immune function and liver function; we performed subgroup analyses and meta-regressions according to the different TACE arms, CKI dosage, composition of CKI, embolizing agents and treatment duration. The safety outcomes were side effects. We conducted pairwise meta-analyses using a random-effects model and then performed random-effects network meta-analyses.
A total of 44 trials, involving 3778 patients and 22 intervention arms, were eligible. TACE+CKI could significantly increase treatment response (1.85, 1.56 to 2.20) and improve therapeutic efficacy based on the secondary outcomes. Significant efficacy was observed in most subgroups. Network meta-analysis revealed that CKI was very suitable for combination treatment when the TACE arm included 5-fluorouracil+epirubicin+hydroxycamptothecin, pirarubicin+hydroxycamptothecin and 5-fluorouracil+pirarubicin+mitomycin+hydroxycamptothecin. The study is registered with PROSPERO (CRD42017073181).
Regarding efficacy, TACE+CKI offers clear advantages for patients with advanced HCC. Moreover, patients should be encouraged to accept CKI, especially when the chemotherapeutic drugs in TACE have high levels of adriamycins (epirubicin and pirarubicin) and hydroxycamptothecin.
通过系统评价和网状Meta分析,评估复方苦参注射液(CKI)联合经动脉化疗栓塞术(TACE)治疗晚期肝细胞癌(HCC)患者的相对疗效和安全性,并确定使用CKI的最佳条件。
我们基于随机对照试验进行了网状Meta分析。检索数据库中截至2017年8月发表的研究。预先设定的主要疗效指标为治疗反应,次要疗效指标为KPS评分、Child-Pugh评分、总生存率、临床症状以及免疫功能和肝功能的改善情况;我们根据不同的TACE方案、CKI剂量、CKI成分、栓塞剂和治疗持续时间进行亚组分析和Meta回归。安全性指标为副作用。我们使用随机效应模型进行成对Meta分析,然后进行随机效应网状Meta分析。
共有44项试验符合条件,涉及3778例患者和22个干预组。TACE+CKI可显著提高治疗反应(1.85,1.56至2.20),并基于次要指标提高治疗效果。在大多数亚组中观察到显著疗效。网状Meta分析显示,当TACE方案包括5-氟尿嘧啶+表柔比星+羟基喜树碱、吡柔比星+羟基喜树碱以及5-氟尿嘧啶+吡柔比星+丝裂霉素+羟基喜树碱时,CKI非常适合联合治疗。该研究已在PROSPERO注册(CRD42017073181)。
在疗效方面,TACE+CKI对晚期HCC患者具有明显优势。此外,应鼓励患者接受CKI,尤其是当TACE中的化疗药物含有高剂量阿霉素(表柔比星和吡柔比星)和羟基喜树碱时。