Cantonal Hospital St. Gallen, Department of Surgery, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland.
Expert Opin Drug Metab Toxicol. 2011 Feb;7(2):201-11. doi: 10.1517/17425255.2011.543674.
The first human exposure to a new medicine always carries a major risk. Assessment of the safety profile and determination of a therapeutic dose are formidable tasks, particularly in oncology where toxicity is seen as a surrogate for efficacy. Increasing evidence supports the adoption of innovative dose-toxicity models, as these are safer and more efficient in meeting the challenges of modern investigational oncology than traditional models used in Phase I clinical trials.
A literature review on dose-toxicity models in oncology was carried out. The objective of this study was to provide a non-mathematical, reader-friendly overview of current and innovative dose-toxicity models in oncology with an emphasis on recent clinical advances, including the benefits of a Bayesian framework.
Innovative dose-toxicity models attempt to minimize clinical risk and maximize research performance. Of these, the Bayesian Continual Reassessment Method and the Escalation With Overdose Control are two successful contemporary designs that outperformed traditional models in clinical trials; they account for patient heterogeneity, combination therapy, and they appropriately assess molecularly targeted agents. Support by regulatory authorities is providing an additional incentive to the widespread use of innovative and efficient dose-toxicity designs: this will improve investigational oncology, and ultimately benefit patients and science alike.
首次接触一种新药总是存在重大风险。评估安全性概况并确定治疗剂量是一项艰巨的任务，特别是在肿瘤学领域，毒性被视为疗效的替代指标。越来越多的证据支持采用创新的剂量-毒性模型，因为这些模型比传统的 I 期临床试验中使用的模型在应对现代肿瘤学研究的挑战时更安全、更高效。
对肿瘤学中的剂量-毒性模型进行了文献回顾。本研究的目的是提供一个非数学的、读者友好的概述，介绍当前和创新的肿瘤学剂量-毒性模型，重点介绍最近的临床进展，包括贝叶斯框架的好处。
创新的剂量-毒性模型试图将临床风险降至最低，同时将研究绩效最大化。其中，贝叶斯连续评估法和递增加量控制法是两种成功的现代设计，它们在临床试验中优于传统模型；它们考虑了患者异质性、联合治疗，并适当地评估了分子靶向药物。监管机构的支持为广泛使用创新和高效的剂量-毒性设计提供了额外的动力：这将改善肿瘤学研究，最终使患者和科学界受益。
