Salzberg Marc
Medpace Inc., Cincinnati, OH, USA and Università degli Studi, Milan, Italy.
Rambam Maimonides Med J. 2012 Apr 30;3(2):e0007. doi: 10.5041/RMMJ.10074. Print 2012 Apr.
Phase 1 first-in-human studies with anti-cancer products differ from other phase 1 studies in that they are evaluated in patients rather than healthy volunteers. The rationale design of targeted drugs triggers changes in the design of these studies. Patient populations are more precisely defined and pose a challenge to the efficient inclusion of study patients. Objectives shift from the definition of a maximum tolerated dose to the evaluation of a recommended phase 2 dose. Other challenges related to the efficacy and safety profile of novel targeted anti-cancer drugs call for changes in designing first-in-human studies, such as definitions of biological doses, collection of fresh tumor tissue for surrogate marker analyses, and the management of infusion-related reactions with monoclonal antibodies. Consequently, the conduct of phase 1 clinical trials in oncology requires changes. Corresponding education with particular focus on phase 1 trials and on the complex drug development process needs to be an integrated part of the medical oncology curriculum for physicians and nursing staff. This is a crucial element for institutions to remain or become clinical research sites for phase 1 studies, and to participate in the drug development process of novel anti-cancer compounds in the future.
抗癌产品的1期首次人体研究与其他1期研究不同，因为这些研究是在患者而非健康志愿者中进行评估。靶向药物的合理设计引发了这些研究设计的变化。患者群体得到了更精确的定义，这对高效纳入研究患者构成了挑战。目标从确定最大耐受剂量转变为评估推荐的2期剂量。与新型靶向抗癌药物的疗效和安全性相关的其他挑战要求在设计首次人体研究时做出改变，例如生物剂量的定义、收集新鲜肿瘤组织进行替代标志物分析以及处理单克隆抗体相关的输注反应。因此，肿瘤学1期临床试验的开展需要做出改变。针对医生和护理人员的医学肿瘤学课程应将特别关注1期试验和复杂药物研发过程的相应教育作为一个组成部分。这是机构保持或成为1期研究临床研究站点，并在未来参与新型抗癌化合物药物研发过程的关键要素。
