Department of Medicine and Breast Cancer Research Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Clin Breast Cancer. 2010;10 Suppl 1(Suppl 1):E23-31. doi: 10.3816/CBC.2010.s.004.
Angiogenesis, which is crucial for the growth and spread of cancer cells, has become an important target for antineoplastic therapies in a variety of malignant tumors. Vascular endothelial growth factor and its receptor promote formation of new blood vessels in tumors. Several drugs, most notably the monoclonal antibody bevacizumab, have been developed to inhibit this process. Clinical trials utilizing bevacizumab and other antiangiogenic drugs in metastatic breast cancer have demonstrated enhanced response rates and prolonged progression-free survival, though no overall survival benefit has been seen. Trials are now under way exploring the use of antiangiogenic agents in patients with early stage breast cancer. We performed a comprehensive review of the published literature (English language), US National Institutes of Health clinical trials registry (ClinicalTrials.gov), and established cooperative groups that revealed approximately 75 clinical trials, completed or ongoing, utilizing antiangiogenic drugs in early-stage breast cancer. A number of phase II trials in the neoadjuvant setting have reported preliminary results suggesting response rates similar to those seen with traditional anthracycline-plus-taxane combination regimens. Most of these early trials have not yet met any survival endpoints. Studies are also ongoing in the adjuvant setting, and these have not yet been reported. The toxicities associated with these agents are similar to those that have been reported in the metastatic trials. Most of these side effects are grade 1 or 2 and are easily manageable; however, there remain a small percentage of patients who sustain life-threatening vascular events, bleeding, or wound-healing complications. This number is significantly higher in patients receiving antiangiogenic drugs when compared with controls. While we eagerly await completion and results of this impressive portfolio of studies in early breast cancer with antiangiogenic agents, there is an urgent need for a more rational patient/antiangiogenic therapy selection with greater insight into predictive factors for toxicities, therapy efficacy, and clinical benefit.
血管生成对于癌细胞的生长和扩散至关重要，已成为多种恶性肿瘤抗肿瘤治疗的重要靶点。血管内皮生长因子及其受体促进肿瘤中新血管的形成。已经开发了几种药物，特别是单克隆抗体贝伐珠单抗，以抑制这一过程。在转移性乳腺癌中利用贝伐珠单抗和其他抗血管生成药物的临床试验表明，反应率提高，无进展生存期延长，但并未观察到总生存期获益。目前正在进行临床试验，探索抗血管生成药物在早期乳腺癌患者中的应用。我们对已发表的文献（英文）、美国国立卫生研究院临床试验注册处（ClinicalTrials.gov）和已建立的合作组进行了全面回顾，发现大约有 75 项临床试验已经完成或正在进行，这些试验使用了抗血管生成药物治疗早期乳腺癌。一些新辅助治疗的 II 期临床试验报告了初步结果，表明反应率与传统蒽环类药物加紫杉烷联合方案相似。这些早期试验中的大多数尚未达到任何生存终点。在辅助治疗中也正在进行研究，但尚未报告。这些药物的毒性与转移性试验中报告的毒性相似。大多数副作用为 1 级或 2 级，易于管理；然而，仍有一小部分患者发生危及生命的血管事件、出血或伤口愈合并发症。与对照组相比，接受抗血管生成药物治疗的患者中，这一数字明显更高。虽然我们急切地等待着抗血管生成药物在早期乳腺癌中的这一系列令人印象深刻的研究的完成和结果，但迫切需要更合理地选择患者/抗血管生成治疗方案，并深入了解毒性、治疗效果和临床获益的预测因素。
