Ding K, Pater J, Whitehead M, Seymour L, Shepherd F A
National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston, ON, Canada.
Contemp Clin Trials. 2008 Jul;29(4):527-36. doi: 10.1016/j.cct.2008.01.004. Epub 2008 Jan 19.
The target of novel signal transduction inhibitors may be present on normal as well as tumor cells, resulting in mechanistic adverse effects (AE) in addition to antitumor activity. As those AEs lie in the causal pathway that patients respond to the drug, may thus serve as an indicator of benefit from the drug. In this paper, we discuss issues in validating drug related AEs as predictive markers of overall survival benefit. Based on our proposed approach, we showed that erlotinib induced skin rash appears to predict a survival benefit.
新型信号转导抑制剂的靶点可能存在于正常细胞和肿瘤细胞上，除了抗肿瘤活性外，还会导致机制性不良反应（AE）。由于这些不良反应处于患者对药物产生反应的因果途径中，因此可能作为药物获益的指标。在本文中，我们讨论了将与药物相关的不良反应验证为总生存获益预测标志物的相关问题。基于我们提出的方法，我们发现厄洛替尼引起的皮疹似乎可预测生存获益。
