VEGF as a Marker for Outcome Among Advanced Breast Cancer Patients Receiving anti-VEGF Therapy with Bevacizumab and Vinorelbine Chemotherapy
VEGF as a Marker for Outcome Among Advanced Breast Cancer Patients Receiving anti-VEGF Therapy with Bevacizumab and Vinorelbine Chemotherapy
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DOI：
10.1158/1078-0432.ccr-08-0593
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发表时间：
2008-12-01
影响因子：
11.5
通讯作者：
Winer, Eric P.
中科院分区：
文献类型：
--
作者：
Burstein, Harold J.;Chen, Yu-Hui;Winer, Eric P.
背景：抗血管内皮细胞生长因子治疗是一种重要的肿瘤新治疗方法。我们试图确定人源化抗血管内皮生长因子单抗、贝伐单抗和长春瑞滨治疗难治性乳腺癌的疗效和安全性，并探讨血浆血管内皮生长因子作为治疗结果预测因子的作用。实验设计：符合条件的患者接受过一到两个化疗方案的转移性乳腺癌或在辅助治疗12个月内复发，且有可测量的疾病和足够的终末器官功能。患者接受贝伐单抗10 mg/kg，每2周一次，长春瑞滨每周一次，直到肿瘤进展或出现禁止性毒性。结果：在接受方案治疗的56名妇女中，贝伐单抗和长春瑞滨的有效率为34%(95%可信区间，22-48%)，中位进展时间为5.5个月。无论肿瘤激素受体状态或先前化疗的类型或程度如何，均可观察到活性。副作用包括不复杂的中性粒细胞减少、高血压、鼻塞/鼻出血和神经病变，这与各自药物的副作用描述一致。三名患者在手术后伤口愈合受损。只有罕见的血栓形成或临床上有意义的蛋白尿。结论：贝伐单抗和长春瑞滨治疗难治性乳腺癌耐受性好，疗效确切。血浆血管内皮生长因子作为接受抗血管内皮生长因子治疗的晚期乳腺癌患者治疗结果的预后标记物，有进一步的评估价值。
Background: Anti-vascular endothelial growth factor therapy (VEGF) is an important new treatment modality in oncology.We sought to determine the efficacy and safety of the humanized monoclonal anti-VEGF antibody, bevacizumab, and vinorelbine as treatment for refractory breast cancer and to explore the role of plasma VEGF as a predictor of treatment outcome.Experimental Design: Eligible patients had received one or two prior chemotherapy regimens for metastatic breast cancer or recurred within 12 months of adjuvant therapy and had measurable disease and adequate end-organ function. Patients received bevacizumab 10 mg/kg every 2 weeks, and vinorelbine each week, until tumor progression or prohibitive toxicity. Plasma VEGF was measured at baseline.Results: Among 56 women treated on protocol, bevacizumab and vinorelbine yielded a 34% response rate (95% confidence interval, 22-48%) and median time to progression of 5.5 months. Activity was observed regardless of tumor hormone receptor status or type or extent of prior chemotherapy. Side effects included uncomplicated neutropenia, hypertension, nasal congestion/epistaxis, and neuropathy, consistent with well-described side effects of the respective agents. Three patients had impaired wound healing following surgical procedures. There were only rare instances of thrombosis or clinically significant proteinuria. Lower levels of baseline VEGF were associated with longer time to progression.Conclusions: Bevacizumab and vinorelbine are well tolerated and effective as treatment for refractory breast cancer. Plasma VEGF warrants further evaluation as a prognostic marker for treatment outcome in advanced breast cancer patients receiving anti-VEGF therapy.