PDF(Pubmed)
Abstract：
BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations.
METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment.
RESULTS: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment.
CONCLUSIONS: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia.
BACKGROUND: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.
METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment.
RESULTS: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment.
CONCLUSIONS: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia.
BACKGROUND: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.
摘要：
背景：发现抗病毒药物Nirmatrelvir是在COVID-19感染期控制肺炎进展的关键药物。然而,对于患有病毒性肺炎的癌症患者，有效治疗的选择很少。糖皮质激素是控制肺炎的有效手段之一,但是有很多不良事件。EGCG是一种具有抗炎功能的天然低毒化合物。因此，本研究旨在研究表没食子儿茶素没食子酸酯(EGCG)气雾剂在癌症人群中控制COVID-19肺炎的安全性和有效性.
方法：本研究设计为前瞻性，单臂,山东省肿瘤医院和研究所的开放标签I/II期试验，2023年1月5日至2023年3月31日期间，病毒性肺炎在确诊新型冠状病毒感染后出现影像学征象。这些患者每天三次用EGCG雾化治疗10ml，持续至少七天。EGCG浓度从1760-8817umol/L增加到4个水平，剂量增加后，每个水平3-6名患者的标准I期设计。由EGCG引起的任何等级不良事件被认为是剂量限制性毒性(DLT)。最大耐受剂量（MTD）定义为最高剂量，其中少于三分之一的患者由于EGCG而经历剂量限制性毒性（DLT）。主要终点是EGCG的毒性和CT表现，前者按不良事件通用术语标准(CTCAE)v.0进行分级。次要终点是治疗前后的实验室参数。
结果：共有60名具有重症COVID-19肺炎高危因素的患者（如老年，吸烟和合并并发症)纳入本I-II期研究。最终分析的54例患者经病理证实有肿瘤负担，并完成了整个治疗过程。据报道，在第二或第三剂量梯度下，患者的屈曲水平为1760umol/L，没有与EGCG相关的急性毒性。在剂量递增至8817umol/L时，2例患者发生恶心和胃部不适的1级不良事件,在1小时内自发解决。经过一周的治疗，CT显示非进展性肺炎的发生率为82%(32/39),肺炎好转率为56.4%(22/39)。与炎症相关的实验室参数没有显着差异（白细胞计数，淋巴细胞计数,IL-6,铁蛋白,C反应蛋白和乳酸脱氢酶）治疗前后。
结论：雾化吸入EGCG的耐受性良好，对癌症人群的初步调查表明，EGCG可能对COVID-19引起的肺炎有效，这可以促进中度肺炎患者的病情改善或防止其发展为重症肺炎。
背景：ClinicalTrials.gov标识符：NCT05758571。注册日期：2023年2月8日。
方法：本研究设计为前瞻性，单臂,山东省肿瘤医院和研究所的开放标签I/II期试验，2023年1月5日至2023年3月31日期间，病毒性肺炎在确诊新型冠状病毒感染后出现影像学征象。这些患者每天三次用EGCG雾化治疗10ml，持续至少七天。EGCG浓度从1760-8817umol/L增加到4个水平，剂量增加后，每个水平3-6名患者的标准I期设计。由EGCG引起的任何等级不良事件被认为是剂量限制性毒性(DLT)。最大耐受剂量（MTD）定义为最高剂量，其中少于三分之一的患者由于EGCG而经历剂量限制性毒性（DLT）。主要终点是EGCG的毒性和CT表现，前者按不良事件通用术语标准(CTCAE)v.0进行分级。次要终点是治疗前后的实验室参数。
结果：共有60名具有重症COVID-19肺炎高危因素的患者（如老年，吸烟和合并并发症)纳入本I-II期研究。最终分析的54例患者经病理证实有肿瘤负担，并完成了整个治疗过程。据报道，在第二或第三剂量梯度下，患者的屈曲水平为1760umol/L，没有与EGCG相关的急性毒性。在剂量递增至8817umol/L时，2例患者发生恶心和胃部不适的1级不良事件,在1小时内自发解决。经过一周的治疗，CT显示非进展性肺炎的发生率为82%(32/39),肺炎好转率为56.4%(22/39)。与炎症相关的实验室参数没有显着差异（白细胞计数，淋巴细胞计数,IL-6,铁蛋白,C反应蛋白和乳酸脱氢酶）治疗前后。
结论：雾化吸入EGCG的耐受性良好，对癌症人群的初步调查表明，EGCG可能对COVID-19引起的肺炎有效，这可以促进中度肺炎患者的病情改善或防止其发展为重症肺炎。
背景：ClinicalTrials.gov标识符：NCT05758571。注册日期：2023年2月8日。
