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

贝伐珠单抗/西妥昔单抗/伊立替康或贝伐珠单抗/西妥昔单抗治疗结直肠癌

• 批准号: 7378324
• 负责人: HOWARD S HOCHSTER
• 金额: $ 2.24万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378324
• 关键词: BEVACIZUMAB; CETUXIMAB; IRINOTECAN; COLORECTAL; CANCER

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一项比较贝伐珠单抗联合西妥昔单抗+伊立替康与单用西妥昔单抗治疗伊立替康难治性结直肠癌的随机II期试验。该试验由Memorial Sloan-Kettering管理。“理想的”标准一线和二线治疗结直肠癌目前有争议，伊立替康或奥沙利铂联合5-FU和亚叶酸的证据是有利的。二线治疗通常是与第一轮中未使用的药物联合使用。本方案将评价贝伐珠单抗联合西妥昔单抗作为一线和二线药物治疗方案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。贝伐珠单抗联合IFL的最新研究结果显示，将其添加到方案中具有显著的临床获益，因此有信心在此重现。西妥昔单抗阻断EGF和TGF-α与EGFR的结合，并抑制配体诱导的该酪氨酸激酶受体的活化。与伊立替康联合使用和单独使用，缓解率分别为~22%和~11%。因此，有充分的理由将这些措施结合起来进行尝试，并期待取得成功。由于伊立替康是毒性的主要来源，因此研究的第二组测试是否可以在不显著损失益处的情况下停用该药物。这项研究建立在最近贝伐单抗/IFL试验的优异结果的基础上，通过添加具有预期互补活性的药物。相关研究将关注基因表达水平，以及在同意的患者中，与每种治疗方法中的无进展生存期、肿瘤缓解、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对个体患者的治疗。