BEVACIZUMAB AND DOCETAXEL FOR LOCALLY ADVANCED BREAST CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究探讨了贝伐单抗和多西他赛治疗局部晚期（IIIa期和IIIb期）乳腺癌的主要治疗方法。两种药物都以血管生成为目标，临床前数据支持有益的抗肿瘤作用，因此该方案的主要假设是，与单独接受多西紫杉醇治疗的患者相比，接受联合治疗的患者预期有更大比例的病理疾病反应。有反应的患者应表现为肿瘤微血管密度降低，肿瘤凋亡增加，mri肿瘤灌注减少。核簇蛋白/XIP8表达增强的肿瘤患者对贝伐单抗和多西他赛的临床和病理反应应该增强。所有患者将在入组时随机接受多西他赛单独治疗或多西他赛联合贝伐单抗治疗。所有患者将接受两个8周周期的治疗，包括每周多西他赛6周，休息2周。那些随机分配到贝伐单抗的患者也将每2周不间断地接受贝伐单抗治疗。两个周期后，病情稳定或反应性疾病的患者将接受最终的乳房手术。所有患者在手术后都将接受明确的放射治疗。放射治疗后将进行进一步的化疗。雌激素和/或孕激素受体阳性疾病患者将在放疗后化疗完成后接受5年的他莫昔芬每日20mg口服治疗。

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 study investigates primary therapy with bevacizumab and docetaxel for locally advanced (Stage IIIa and IIIb) breast cancer. Both drugs target angiogenesis, and pre-clinical data support a beneficial anti-tumor effect, therefore the primary hypothesis of this protocol is that a greater percentage of patients receiving combination therapy are expected to have a pathologic disease response compared with those patients receiving docetaxel alone. The responding patients should exhibit a reduction in tumor microvascular density, increased tumor apoptosis, and decreased MRI-tumor perfusion. Patients with tumors exhibiting enhanced expression of nuclear clusterin/XIP8 should demonstrate enhanced clinical and pathologic response to bevacizumab and docetaxel administration. All patients will be randomized at entry to either docetaxel alone or docetaxel with bevacizumab. All patients will receive two 8-week cycles consisting of docetaxel weekly for six weeks with a two-week break. Those patients randomized to bevacizumab will also receive bevacizumab every 2 weeks without break. After two cycles, patients with stable or responsive disease will undergo definitive breast surgery. All patients will receive definitive radiation therapy following surgery. Further chemotherapy will follow radiation therapy. Patients with estrogen and/or progesterone receptor positive disease will receive five years of Tamoxifen 20 mg daily oral therapy following completion of post-radiation chemotherapy.