Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study

Abstract

BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size.

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases?

“…Besides benefits of EGCG for prevention of cancer and mitigation of its development and metastasis, EGCG may also be valuable for prevention of adverse effects of radiotherapy due to lung cancer as recently demonstrated in Phase 2 Clinical Trial (NCT02577393) [ 227 ].…”

The radio-protective effects of (-)- Epigallocatechin-3-gallate (EGCG): regulating macrophage function in radiation-induced intestinal injury

“…In vitro and animal models, the use of EGCG has been shown to inhibit a high variety of cancer processes (Singh et al, 2011). In vivo studies, EGCG acts as a radiosensitizer to synergize the treatment of cancer (Lecumberri et al, 2013), and also be able to ameliorates the adverse side effects derived from cancer therapy (Li X et al, 2020; Zhao et al, 2016; Zhu et al, 2016; Zhu et al, 2020; Zhu et al, 2021). Previous studies have revealed that treatment with EGCG protects rodents from intestinal damage after TBI up to 9 Gy (Emami et al, 2014).…”

“…EGCG has been demonstrated to ameliorate esophagitis (Li X et al, 2020;Zhu et al, 2021), oral mucositis (Zhu et al, 2020), and acute skin damage (Zhao et al, 2016;Zhu et al, 2016) induced by radiation in clinical trials, which suggests that it has a prospect in clinical application. Xie LW et al (Xie et al, 2020) have investigated the effects of EGCG on RIII and revealed the key role of ROS and Nrf-2 in the radioprotection in intestinal epithelial cells.…”

“…(-)-Epigallocatechin-3-gallate (EGCG), a major bioactive catechin derived from green tea (Stenvang et al, 2016), has numerous biological activities, such as anti-bacterial (Reygaert, 2018; Steinmann et al, 2013), anti-inflammatory (Wang et al, 2021; Zhong et al, 2012), and radioprotective activities (Kępka et al, 2019; Yi et al, 2020). EGCG has been demonstrated to ameliorate esophagitis (Li X et al, 2020; Zhu et al, 2021), oral mucositis (Zhu et al, 2020), and acute skin damage (Zhao et al, 2016; Zhu et al, 2016) induced by radiation in clinical trials, which suggests that it has a prospect in clinical application. Xie LW et al (Xie et al, 2020) have investigated the effects of EGCG on RIII and revealed the key role of ROS and Nrf-2 in the radioprotection in intestinal epithelial cells.…”

Role of natural products in tumor therapy from basic research and clinical perspectives

“…Accumulating evidence reveals that EGCG has a strong protective effect against lung cancer. Several clinical studies showed that EGCG is a radioprotective agent, prevents radiation-induced esophagitis, and enhances objective response rate (ORR) but without significantly prolonging PFS and OS in lung cancer patients [83,84]. A number of in vitro and in vivo studies have confirmed that EGCG inhibits CSC-like properties and self-renewal ability of lung cancer [85][86][87][88].…”