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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

中文翻译：

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EGCG氧气雾化吸入治疗COVID-19肺炎合并癌症患者疗效和安全性的I/II期临床试验

抗病毒药物 Nirmatrelvir 被发现是在 COVID-19 感染阶段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来说，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，但不良反应较多。 EGCG是一种天然低毒化合物，具有抗炎功能。因此，本研究旨在调查表没食子儿茶素-3-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。该研究被设计为一项前瞻性、单臂、开放标签的 I/II 期试验，于 2023 年 1 月 5 日至 2023 年 3 月 31 日在山东省肿瘤医院和研究所进行，针对确诊的新型冠状病毒感染后的病毒性肺炎的放射学症状。这些患者接受 EGCG 雾化治疗，每次 10 ml，每日 3 次，持续至少 7 天。按照每个水平 3-6 名患者的标准 I 期设计，随着剂量的增加，EGCG 浓度从 1760-8817umol/L 增加到 4 个水平。 EGCG 引起的任何级别不良事件均被视为剂量限制性毒性 (DLT)。最大耐受剂量 (MTD) 定义为不到三分之一的患者因 EGCG 出现剂量限制性毒性 (DLT) 的最高剂量。主要终点是 EGCG 和 CT 结果的毒性，前者根据不良事件通用术语标准 (CTCAE) v. 5.0 进行分级。次要终点是治疗前后的实验室参数。本次I-II期研究共纳入60名具有重症COVID-19肺炎高危因素（如高龄、吸烟和合并并发症等因素）的患者。最终分析54例患者均经病理证实有肿瘤负荷，并完成了整个疗程。据报道，在第二或第三剂量梯度下，一名患者的血压水平为 1760 umol/L，并且没有与 EGCG 相关的急性毒性。当剂量递增至8817umol/L时，两名患者出现恶心和胃部不适的1级不良事件，并在1小时内自行缓解。治疗1周后CT显示肺炎无进展发生率为82%（32/39），肺炎好转率为56.4%（22/39）。治疗前后炎症相关实验室参数（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）无显着差异。 EGCG气雾吸入耐受性良好，在癌症人群中的初步调查表明，EGCG可能对COVID-19诱发的肺炎有效，可以促进中度肺炎患者的好转或阻止其发展为重症肺炎。 ClinicalTrials.gov 标识符：NCT05758571。注册日期：2023年2月8日。