PH I: ORAL GLEEVEC & ONE HR WEEKLY PACLITAXEL INFUSION- METASTATICS SOLID TUMORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 格列卫通过对Bcr-Abl、血小板衍生生长因子受体和C-Kit激活的酪氨酸激酶途径的有效活性，在慢性粒细胞白血病（CML）和胃肠道间质瘤中显示出活性。 紫杉醇通过其对微管组装和稳定微管以防止解聚的作用，对微管具有广泛的抗肿瘤活性，从而通过诱导细胞周期中期-后期部分的持续有丝分裂阻滞来抑制细胞增殖。 先前的临床前研究显示，当其他化疗药物与格列卫联合使用时，具有显著的协同作用，但尚未在此类比较中评估Paclitazone。通过将广泛作用的药物Paclitazone与新药物Gleevec组合，我们可以观察到累加或甚至协同效应，而不会显着增加继发于独立药物机制的毒性。 具体目标： 主要目标： + 确定格列卫和紫杉醇联合治疗晚期肿瘤患者的剂量限制性毒性和最大耐受剂量。 + 描述格列卫和紫杉醇联合给药时的药代动力学特征。 次要目标： + 记录接受格列卫和紫杉醇治疗的患者的任何客观抗肿瘤反应。 + 记录肿瘤活检组织中C-Kit和血小板衍生生长因子受体（PDGF-R）表达与肿瘤对格列卫和紫杉醇联合治疗的反应之间的关系。 其他队列目标： + 记录紫杉烷难治性乳腺癌患者肿瘤活检组织中C-Kit和PDGF-R表达与肿瘤对格列卫和紫杉醇的反应之间的任何关系。 + 在紫杉烷难治性非小细胞肺癌患者中，记录肿瘤活检组织中C-Kit和PDGF-R表达与肿瘤对格列卫和紫杉醇的反应之间的任何关系。 假设：确定这两种潜在的抗血管生成药物联合使用的安全性。

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. Gleevec has shown activity in chronic myeloid leukemia (CML) and gastrointestinal stromal tumors via potent activity against Bcr-Abl, platelet-derived growth factor receptor, and the C-Kit activated tyrosine kinase pathway. Paclitaxel has broad antitumor activity on microtubules via its action on microtubular assembly and stabilization of the microtubules against depolymerization, thereby inhibiting cellular proliferation by inducing a sustained mitotic block at the metaphase-anaphase portion of the cell cycle. Previous preclinical studies have shown significant synergistic effects when other chemotherapy agents have been combined with Gleevec, however Paclitaxel has not been evaluated in such a comparison. By combining the broad acting agent Paclitaxel with the new agent Gleevec we may observe additive or even synergistic effects without significant increases in toxicities secondary to independent antineoplastic mechanisms SPECIFIC AIMS: Primary Aims: + Determine the dose-limiting toxicity and maximum tolerated dose of Gleevec and Paclitaxel when given in combination to patients with advanced tumors. + Characterize the pharmacokinetics of Gleevec and Paclitaxel when given in combination. Secondary Aims: + Document any objective antitumor response in patients treated with Gleevec and Paclitaxel. + Document the relationship between C-Kit and platelet derived growth factor receptor (PDGF-R) expression on tumor biopsies and tumor response to the combination of Gleevec and Paclitaxel. Additional Cohort Objectives: + Document any relationship between C-Kit and PDGF-R expression on tumor biopsies and tumor response to Gleevec and Paclitaxel in Taxane refractory breast cancer patients. + Document any relationship between C-Kit and PDGF-R expression on tumor biopsies and tumor response to Gleevec and Paclitaxel in Taxane refractory Non-Small Cell Lung Cancer patients. Hypothesis: To determine the safety of combining these two potential anti-angiogenic agents.