Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Clin Cancer Res. 2011 Jan 15;17(2):222-8. doi: 10.1158/1078-0432.CCR-10-1402. Epub 2010 Nov 3.
Recently, many agents have been identified that target molecular pathways that can mitigate radiation toxicity. To date, no drugs have been approved as radiation injury mitigators, which are defined as agents administered after irradiation but before toxicity is manifest. In order to accelerate the application of potential mitigators for cancer patients, a meeting sponsored by the National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID) was held in January 2010. This article presents an algorithm to guide clinical trials for such agents in patients receiving radiotherapy or radiochemotherapy. It reviews the mechanisms of radiation injury, the clinical problem, the preclinical and clinical development of candidate agents, and the design and conduct of clinical trials. The central role of patient reported outcomes is outlined, as well as key lessons learned from prior clinical trials. Ultimately, the goal is to be able to apply such promising agents to improve the quality of life for patients receiving radiotherapy or chemoradiotherapy for cancer.
最近，已经鉴定出许多靶向分子途径的药物，这些药物可以减轻辐射毒性。迄今为止，还没有药物被批准为辐射损伤缓解剂，这些药物被定义为在照射后但在毒性显现之前给予的药物。为了加速潜在缓解剂在癌症患者中的应用，美国国立癌症研究所（NCI）和美国国立过敏和传染病研究所（NIAID）于 2010 年 1 月召开了一次会议。本文提出了一种算法，用于指导接受放疗或放化疗的患者使用此类药物的临床试验。它回顾了辐射损伤的机制、临床问题、候选药物的临床前和临床开发，以及临床试验的设计和实施。概述了患者报告结果的核心作用，以及从以前的临床试验中吸取的关键经验教训。最终目标是能够应用这些有前途的药物来改善接受放疗或放化疗的癌症患者的生活质量。
