BEVACIZUMAB/CETUXIMAB/IRINOTECAN OR BEVACIZUMAB/CETUXIMAB IN COLORECTAL CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项随机II期试验，贝伐单抗联合西妥昔单抗+伊立替康vs单独西妥昔单抗治疗伊立替康难治性结直肠癌。试验由斯隆-凯特琳纪念医院管理。目前对“理想”标准的一线和二线结直肠癌治疗仍有争议，有证据表明伊立替康或奥沙利铂联合5-FU和亚叶酸蛋白更受青睐。二线治疗通常是与第一轮未使用的药物联合使用。该方案将评估贝伐单抗联合西妥昔单抗作为一线和二线药物治疗失败后的适当随访治疗。贝伐单抗是一种抗vegf和抗血管生成药物。最近贝伐单抗联合IFL的研究结果显示，将其添加到方案中有显著的临床益处，因此有信心这将在这里重现。西妥昔单抗阻断EGF和TGF-a与EGFR的结合，抑制配体诱导的酪氨酸激酶受体的激活。与伊立替康联合或单独使用，有效率分别为~22%和~11%。因此，我们有充分的理由将这些方法结合起来进行尝试，并期望取得成功。由于伊立替康是毒性的主要来源，研究的第二部分测试了是否可以在不显著损失疗效的情况下停用这种药物。本研究是在贝伐单抗/IFL试验最近取得优异结果的基础上，添加了一种具有预期补充活性的药物。相关研究将着眼于基因表达水平，并在同意的患者中，在每种治疗中与无进展生存期、肿瘤反应、总生存期和毒性相关的种系多态性。在未来，这些数据有望用于更好地调整治疗方案，以针对个别患者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a randomized Phase II trial of Bevacizumab in combination with Cetuximab plus Irinotecan vs with Cetuximab alone in Irinotecan-refractory colorectal cancer. The trial is managed from Memorial Sloan-Kettering. The "ideal" standard first- and second-line treatments for colorectal cancer are currently debated, with evidence for either irinotecan or oxaliplatin in combination with 5-FU and leucovorin being favored. Second-line therapy is usually a combination with the drug not used in the first round. The protocol will evaluate the use of Bevacizumab in combination with Cetuximab as an appropriate follow-up treatment to use after the failure of the first- and second-line drug regimens. Bevacizumab is an anti-VEGF and anti-angiogenic drug. Very recent results from studies with Bevacizumab in combination with IFL showed marked clinical benefit with its addition to the protocol, so there is confidence that this will be reproduced here. Cetuximab blocks binding of EGF and TGF-a to EGFR and inhibits ligand-induced activation of this tyrosine kinase receptor. Used in combination with irinotecan and also alone, response rates of ~22% and ~11% were achieved. There is, therefore, a strong rationale to try these in combination and to expect success. Since irinotecan is a major source of toxicity, the second arm of the study tests whether this drug can be dropped without significant loss of benefit. This study builds on the recent excellent results of the Bevacizumab/IFL trial by adding a drug with an expected complementary activity. Correlative studies will look at gene expression levels and, in consenting patients, germline polymorphisms associated with progression-free survival, tumor response, overall survival and toxicity in each of the treatments to be employed. In the future such data could hopefully be used to better tune treatments to the individual patient.