Clinical benefit from EGFR-TKI plus ginsenoside Rg3 in patients with advanced non-small cell lung cancer harboring EGFR active mutation

Abstract

PurposeAcquired resistance is a bottleneck that restricts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for lung cancer. Ginsenoside Rg3 is an antiangiogenic agent which can down-regulate the expressions of vascular endothelial growth factor (VEGF) and EGFR. Combination of EGFR-TKI and ginsenoside Rg3 may be a promising strategy to delay acquired resistance. This retrospective study explored the efficacy and safety of this combined regimen in patients with EGFR mutation and advanced non-small cell lung cancer (NSCLC).ResultsBy the deadline of March 31th 2016, the median follow-up period reached 22.9 months. The median PFS was significantly longer in group A than in group B (12.4 months vs 9.9 months, P = 0.017). In addition, ORR was significantly higher in group A than in group B (59.6% vs 41.7%, P = 0.049). The median OS in group A showed no extended tendency compared with that in group B (25.4 months vs 21.4 months, P = 0.258). No significant difference in side effects was found between the two groups.MethodsA total of 124 patients with advanced NSCLC and EGFR active mutation were collected and analyzed. All of them were treated with first-line EGFR-TKI and divided into two groups. In group A (n=52), patients were administered EGFR-TKI plus ginsenoside Rg3 at standard doses. In group B (n=72), patients received EGFR-TKI alone. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and side effects were analyzed.ConclusionsGinsenoside Rg3 improves median PFS and ORR of first-line EGFR-TKI treatment in EGFR-mutant advanced NSCLC patients, thus providing a new regimen to delay acquired resistance of EGFR-TKI.

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

“…Patients with advanced NSCLC and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) mutation were recruited in a study that investigated the safety and efficacy of the combined therapy, ginsenoside Rg3 and EGFR-TKI. It was shown that this therapy increased progression-free survival, overall survival and objective response rate compared to EGFR-TKI alone [263]. In another study, the safety and efficacy of combined ginsenoside Rg3 and transcatheter arterial chemoembolization (TACE) were studied in patients with advanced hepatocellular carcinoma.…”

Anti-Angiogenic Properties of Ginsenoside Rg3

“…In healthy humans receiving intramuscular injections of 10–60 mg/kg SRg3 as a single dose or 30 mg/kg once every two days for 15 days the drug was well tolerated with no detectable sign or symptoms of toxicity [ 110 ]. Furthermore, some clinical trials on non-small cell lung carcinoma [ 113 , 114 ] and advanced hepatocellular carcinoma [ 115 ] have used Rg3 as orally administered anti-angiogenic agent, up to 50 mg/day with no reported toxicity [ 113 , 114 , 115 ]. Therefore, Rg3 at these doses appears to be safe and well tolerated.…”

Anticancer drug discovery from Chinese medicinal herbs

“…A study has shown that ginsenoside Rg3 (Fig. 1 n), purified from Ginseng Radix Et Rhizoma , provides a new regimen to delay acquired resistance of EGFR tyrosine kinase inhibitors and ultimately improves median progression-free survival and overall response rate in advanced non-small cell lung cancer patients [ 61 ]. For the patients with acquired resistance, overcoming the resistant status or re-sensitizing the therapeutic effects serve as another strategy.…”