UAB 0461 BEVACIZUMAB TO REVERSE ACQUIRED ESTROGEN INDEPENDENCE IN BREAST CANCER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的主要目标将是确定Bevacizumab能否逆转获得性激素治疗耐药，以进展时间衡量，并评估激素治疗与Bevacizumab联合使用的毒性。次要目标包括确定应答率和18F-FDG PET扫描“代谢反应”与客观应答率和反应参数持续时间的相关性。据推测，肿瘤细胞血管内皮生长因子的上调是逆转激素反应性乳腺癌患者雌激素依赖的重要机制，从而导致先前激素治疗有效的患者的肿瘤进展，而在激素治疗中添加抗血管内皮生长因子抗体Bevacizumab将逆转这种获得性抵抗。患者必须有可评估的疾病，必须对一线或二线激素治疗有反应并对激素药物产生抗药性，并且ECOG表现状态为0、1或2。在开始治疗之前，患者将进行PET扫描、心功能评估(超声心动图)、标准疾病评估(CT扫描、MRI等)和适当的实验室评估。患者将接受与以前相同的口服激素治疗，此外，还将每3周接受一次贝伐单抗IV注射。在6周时，患者将有第一次反应评估，包括PET扫描。有客观反应或病情稳定的患者将继续采用相同的方案，每6周重新进行一次治疗，或直到观察到病情进展。

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. The primary objectives of this study will be to determine if acquired hormone therapy resistance can be reversed by Bevacizumab, as measured by time to progression and to evaluate toxicity of the combination of hormone treatment plus Bevacizumab. Secondary objectives include determining response rate and correlating 18F-FDG PET scan "metabolic response" with objective response rate and duration of response parameters. It is hypothesized that up-regulation of tumor cell VEGF is an important mechanism to subvert estrogen dependence in hormone responsive breast cancer patients resulting in tumor progression in patients previously responding to hormonal therapy, and the addition of an anti-VEGF antibody, Bevacizumab, to the hormonal therapy will reverse this acquired resistance. To be enrolled, patients must have evaluable disease, must have responded to first or second line hormonal therapy and became resistant to the hormonal agent, and ECOG performance status 0, 1 or 2. Prior to starting therapy, patients will have a PET scan, evaluation of heart function (echocardiogram), standard disease assessments (CT scans, MRI, etc.), and appropriate laboratory evaluations. Patients will take the same oral hormonal therapy they had taken previously and in addition, will receive Bevacizumab IV infusions every 3 weeks. At 6 weeks patients will have the first evaluation of response including a PET scan. Patients with objective response or stable disease will continue the same regimen with restaging every 6 weeks or until progression is observed.