Chmil Vojtěch, Filipová Alžběta, Tichý Aleš
Department of Radiobiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Int J Radiat Biol. 2023;99(8):1148-1166. doi: 10.1080/09553002.2023.2173822. Epub 2023 Feb 6.
Ionizing radiation (IR) is widely applied in radiotherapy for the treatment of over 50% of cancer patients. IR is also intensively used in medical diagnostics on a daily basis in imaging. Moreover, recent geopolitical events have re-ignited the real threat of the use of nuclear weapons. Medical radiation countermeasures represent one of the effective protection strategies against the effects of IR. The aim of this review was to summarize the most commonly used strategies and procedures in the development of radiation countermeasures and to evaluate the current state of their research, with a focus on those in the clinical trial phase.
Clinical trials for this review were selected in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was performed in the clinicaltrials.gov database as of May 2022.
Our search returned 263 studies, which were screened and of which 25 were included in the review. 10 of these studies had been completed, 3 with promising results: KMRC011 increased G-CSF, IL-6, and neutrophil counts suggesting potential for the treatment of hematopoietic acute radiation syndrome (H-ARS); GC4419 reduced the number of patients with severe oral mucositis and its duration; the combination of enoxaparin, pentoxifylline, and ursodeoxycholic acid reduced the incidence of focal radiation-induced liver injury.
The agents discovered so far show significant side effects or low efficacy, and hence most of the tested agents terminate in the early stages of development. In addition, the low profitability of this type of drug demotivates the private sector to invest in such research. To overcome this problem, there is a need to involve more public resources in funding. Among the technological opportunities, a deeper use of approaches seems to be prospective.
电离辐射(IR)广泛应用于放射治疗,超过50%的癌症患者接受该治疗。IR还每天大量用于医学诊断成像。此外,近期的地缘政治事件再次引发了使用核武器的现实威胁。医学辐射对策是抵御IR影响的有效保护策略之一。本综述的目的是总结辐射对策研发中最常用的策略和程序,并评估其研究现状,重点关注处于临床试验阶段的对策。
本综述的临床试验根据系统评价和Meta分析的首选报告项目(PRISMA)声明进行选择。检索截至2022年5月的clinicaltrials.gov数据库。
我们的检索返回了263项研究,经过筛选,其中25项纳入本综述。这些研究中有10项已经完成,3项结果有前景:KMRC011增加了粒细胞集落刺激因子、白细胞介素-6和中性粒细胞计数,表明其在治疗造血急性放射综合征(H-ARS)方面具有潜力;GC4419减少了严重口腔黏膜炎患者的数量及其持续时间;依诺肝素、己酮可可碱和熊去氧胆酸联合使用降低了局灶性放射性肝损伤的发生率。
目前发现的药物显示出明显的副作用或低疗效,因此大多数受试药物在研发早期就终止了。此外,这类药物的低盈利性降低了私营部门投资此类研究的积极性。为克服这一问题,需要更多公共资源投入资金。在技术机遇方面,更深入地使用某些方法似乎具有前瞻性。