Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer

DOI record: { "DOI": "10.1186/s12885-024-12228-3", "ISSN": [ "1471-2407" ], "URL": "http://dx.doi.org/10.1186/s12885-024-12228-3", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Result</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Trial registration</jats:title>\n <jats:p>ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.</jats:p>\n </jats:sec>", "alternative-id": [ "12228" ], "article-number": "486", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "14 November 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "5 April 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "17 April 2024" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "This study was approved by the Institutional Review and Ethical Committees at the affiliated Cancer Hospital of Shandong first Medical University and registered at ClinicalTrials.gov (NCT057-58571). Informed consent was provided by every participant." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "The authors declare no competing interests." } ], "author": [ { "affiliation": [], "family": "Yin", "given": "Xiaoyan", "sequence": "first" }, { "affiliation": [], "family": "Zhu", "given": "Wanqi", "sequence": "additional" }, { "affiliation": [], "family": "Tang", "given": "Xiaoyong", "sequence": "additional" }, { "affiliation": [], "family": "Yang", "given": "Guangjian", "sequence": "additional" }, { "affiliation": [], "family": "Zhao", "given": "Xianguang", "sequence": "additional" }, { "affiliation": [], "family": "Zhao", "given": "Kaikai", "sequence": "additional" }, { "affiliation": [], "family": "Jiang", "given": "Liyang", "sequence": "additional" }, { "affiliation": [], "family": "Li", "given": "Xiaolin", "sequence": "additional" }, { "affiliation": [], "family": "Zhao", "given": "Hong", "sequence": "additional" }, { "affiliation": [], "family": "Wang", "given": "Xin", "sequence": "additional" }, { "affiliation": [], "family": "Yan", "given": "Yuanyuan", "sequence": "additional" }, { "affiliation": [], "family": "Xing", "given": "Ligang", "sequence": "additional" }, { "affiliation": [], "family": "Yu", "given": "Jinming", "sequence": "additional" }, { "affiliation": [], "family": "Meng", "given": "Xiangjiao", "sequence": "additional" }, { "affiliation": [], "family": "Zhao", "given": "Hanxi", "sequence": "additional" } ], "container-title": "BMC Cancer", "container-title-short": "BMC Cancer", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 4, 17 ] ], "date-time": "2024-04-17T08:29:24Z", "timestamp": 1713342564000 }, "deposited": { "date-parts": [ [ 2024, 4, 17 ] ], "date-time": "2024-04-17T08:30:49Z", "timestamp": 1713342649000 }, "funder": [ { "DOI": "10.13039/501100001809", "award": [ "81972863", "No.81972796" ], "doi-asserted-by": "publisher", "name": "National Natural Science Foundation of China" }, { "award": [ "ZR201911040452" ], "name": "the foundation of Natural Science Foundation of Shandong" }, { "award": [ "Y-HS202102-0089" ], "name": "CSCO-Haosen Foundation" } ], "indexed": { "date-parts": [ [ 2024, 4, 18 ] ], "date-time": "2024-04-18T02:22:29Z", "timestamp": 1713406949610 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 4, 17 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 4, 17 ] ], "date-time": "2024-04-17T00:00:00Z", "timestamp": 1713312000000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 4, 17 ] ], "date-time": "2024-04-17T00:00:00Z", "timestamp": 1713312000000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s12885-024-12228-3.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s12885-024-12228-3/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s12885-024-12228-3.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2024, 4, 17 ] ] }, "published-online": { "date-parts": [ [ 2024, 4, 17 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1001/jama.2020.12839", "author": "WJ Wiersinga", "doi-asserted-by": "publisher", "first-page": "782", "issue": "8", "journal-title": "Jama Aug", "key": "12228_CR1", "unstructured": "Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC, Pathophysiology. 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