PREOPERATIVE TREATMENT OF LUNG CANCER WITH rhuMab VEGF

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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.