Bo Zhou, Jianhua Wang, Zhiping Yan, Rong Liu, Sheng Qian, Xudong Qu, Liang Zhu, Jiemin Cheng, Gaoquan Gong, Yi Chen, Qingxin Liu, Jianjun Luo, Lingxiao Liu, Wen Zhang, Changyu Li, Wei Zhang

Interventional Radiology, Fudan University Zhongshan Hospital

Objective:This single-center, open-label, randomized, controlled trial aimed to evaluate the efficacy and safety of ginsenoside Rg3, a low toxicity vascular-endothelial growth factor (VEGF) inhibitor, when used to supplement transarterial chemoembolization (TACE). Method: Advanced hepatocellular carcinoma (HCC) patients with no prior systemic therapy were randomly divided to receive two daily oral Rg3doses at 20 mg in combination with TACE (n=152) or TACE alone (n=76). The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), time to untreatable progression (TTUP), disease control rate (DCR), and safety. Result:Median overall survival was 13.2 months (95%CI 11.15-15.26) in the TACE+Rg3 group and 10.1 months (95%CI9.14-11.06) for patients receiving TACE alone (HR 0.63 [95%CI 0.46-0.85],P=0.002). Median TTP values were 4.3 (95%CI 3.32-5.28) and 3.2 (95%CI2.51-3.89) months for TACE+Rg3 and TACE patients, respectively, (HR 0.82 [95%CI0.62-1.08], P=0.151). TACE+Rg3 treated patients had greater median TTUP (8.3months [95%CI 7.05-9.55]) compared with 7.3 months [95%CI 6.40-8.20] obtained for the TACE group, (HR 0.76 [95%CI 0.57-1.02], P=0.063). The most frequently reported Rg3-related grade 3/4 adverse events (constipation, 1.3%; hypertension, 3.9%) were alleviated by symptomatic treatment. Importantly, Rg3 alleviated some TACE-related adverse syndromes (ascites [23.7 vs 48.7%], anorexia [12.5 vs44.7%], and fatigue [9.9 vs 50.0%], all P<0.01) and blood anomalies (anemia [36.8 vs 51.3%], leukopenia [46.7 vs 76.3%], thrombocytopenia [32.9 vs 50.0%], and hyperbilirubinemia [17.8 vs 34.2%], all P<0.05).Conclusion: In patients with advanced HCC and sufficient liver function, ginsenoside Rg3 improves TACE treatment.

Key Words: Advanced Hepatocellular Carcinoma  Transarterial Chemoembolization