Can Kushen injection combined with TACE improve therapeutic efficacy and safety in patients with advanced HCC? a systematic review and network meta-analysis

// Yingshi Zhang 1 , Fuhai Hui 1 , Yue Yang 1 , Haixiao Chu 1 , Xiaochun Qin 1 , Mingyi Zhao 1 and Qingchun Zhao 1, 2 1 Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China 2 Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, P.R. China Correspondence to: Qingchun Zhao, email: zhaoqingchun1967@163.com Mingyi Zhao, email: zmy_dl@126.com Keywords: transarterial chemoembolization, TACE, compound Kushen injection, advanced hepatocellular carcinoma, network meta-analysis Received: August 02, 2017      Accepted: August 28, 2017      Published: September 15, 2017 ABSTRACT Objective: 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. Materials and Methods: 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. Results: 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). Conclusions: 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.