Prospective Study of Transcatheter Arterial Chemoembolization (TACE) with Ginsenoside Rg3 versus TACE Alone for the Treatment of Patients with Advanced Hepatocellular Carcinoma

Abstract

Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may prolong overall survival when compared with TACE alone. (©) RSNA, 2016.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…In another study, the safety and efficacy of combined ginsenoside Rg3 and transcatheter arterial chemoembolization (TACE) were studied in patients with advanced hepatocellular carcinoma. The results showed that this therapy ameliorated TACE-induced adverse effects and prolonged the overall survival compared to the use of TACE alone [264].…”

Ginsenoside Rg3 Alleviates ox-LDL Induced Endothelial Dysfunction and Prevents Atherosclerosis in ApoE−/− Mice by Regulating PPARγ/FAK Signaling Pathway

“…Ginsenoside Rg3 is one of the important ginsenosides in ginseng, the pharmacological effects of which mainly focus on treatment of tumor related diseases. A study showed that Rg3 alleviated the adverse reactions of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma, and prolonged the survival of patients (Zhou et al, 2016). Rg3 can restore endothelial dysfunction against cardiotoxicity by inhibiting oxidative damage and apoptosis via Akt-mediated activation of the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway injured by adriamycin (Wang et al, 2015).…”

The Overall Survival of Patients with Hepatocellular Carcinoma Correlates with the Newly Defined Time to Progression after Transarterial Chemoembolization

“…Although many clinical trials of TACE alone or targeted agents in combination with TACE use OS as a primary endpoint, it takes a long time before its effects are proved [11][12][13] . Furthermore, the OS benefit is diluted by prolonged post-progression survival [14] , because post-trial treatments such as intra-arterial infusion chemotherapy, sorafenib, or other trial agents (including regorafenib, lenvatinib, or immunotherapy) can have a chance of marked antitumor effect, resulting in longer post-progression survival irrespective both in the testing and control arms.…”