PREOPERATIVE TREATMENT OF LUNG CANCER WITH rhuMab VEGF

描述（由申请人提供）：全身治疗患者 在过去的25年里，这促使调查人员 评估早期患者术前化疗的益处 疾病在同一时期内， 导致肺癌进展的分子事件导致了新的 旨在干扰关键生长调节的治疗策略 途径。一个密集的临床和科学研究领域是 侵袭性肿瘤募集新血管生长的能力。一个重要 血管生成的途径是通过血管内皮生长因子 血管内皮生长因子（VEGF），其向血管内皮细胞发送促有丝分裂信号。许多 肿瘤通过自主产生VEGF来劫持这一途径。的发展 药物试剂干扰VEGF途径一直是一个主要的 调查员的目标。一种这样的试剂是rhuMAb VEGF，一种重组的， 抗VEGF人源化单克隆抗体。临床前和早期临床 研究支持rhuMAb VEGF可能是一种活性的 抗癌剂（特别是当与 化疗剂）。我们假设，早期治疗 化疗结合抗血管生成策略将显示出增强的 有效性和回报，在理解的分子基础， 肿瘤对这些药物的反应会很大。我们有三个具体目标， 这个提议。1)术前rhuMAb + VEGF的临床研究 可切除的NSCLC的化疗，然后手术切除。2)分析 肿瘤血管生成的组织学和分子标志物（包括VEGF、VEGF 受体、细胞凋亡和肿瘤血管密度）。第三章 组织学和分子标志物与临床缓解的比较， 研究前/治疗后放射学成像（CT和PET扫描）。小心 本研究中收集的临床和生物学信息的比较/分析 也可能会增强我们对肿瘤生长和进展的理解 作为对治疗的反应。

DESCRIPTION (provided by applicant): Systemic treatment of patients with improvements over the last 25 years. This has encouraged investigators to evaluate the benefit of preoperative chemotherapy in patients with early stage disease. Over the same time frame, improvements in the understanding of the molecular events that lead to the progression of lung cancer have led to novel therapeutic strategies designed to interfere with critical growth regulatory pathways. One area of intense clinical and scientific investigation has been the ability of invasive tumors to recruit new blood vessel growth. An important pathway of angiogenesis is through the vascular endothelial growth factor (VEGF) which sends a mitogenic signal to vascular endothelial cells. Many tumors hijack this pathway by autonomously producing VEGF. The development of pharmaceutical reagents to interfere with the VEGF pathway has been a major goal of investigators. One such reagent is rhuMAb VEGF, a recombinant, humanized monoclonal antibody to VEGF. Preclinical and early clinical investigations have supported the hypothesis that rhuMAb VEGF may be an active anti-cancer agent (particularly when administered in combination with chemotherapeutic agents). We hypothesize that earlier treatment with chemotherapy combined with anti-angiogenic strategies will show enhanced efficacy and that the payoff in terms of understanding the molecular basis of tumor response to these agents will be great. We have three specific aims in this proposal. 1) A clinical study of preoperative rhuMAb VEGF plus chemotherapy for resectable NSCLC followed by surgical resection. 2) Analysis of histologic and molecular markers of tumor angiogenesis (including VEGF, VEGF receptors, apoptosis and tumor blood vessel density) in resection specimens. 3) Comparison of histologic and molecular markers with clinical response and pre-study/post-treatment radiographic imaging (CT and PET scanning). Careful comparison/analysis of clinical and biologic information gathered in this study will likely enhance our understanding of tumor growth and progression as well as response to therapy.