Krämer I, Lipp H-P
Johannes Gutenberg-University Hospital, Mainz, Germany.
J Clin Pharm Ther. 2007 Feb;32(1):1-14. doi: 10.1111/j.1365-2710.2007.00800.x.
Angiogenesis is the process by which new blood vessels are created from pre-existing vessels. It is essential for the growth and development of normal cells and tissues during embryonic and neonatal development and of tumour cells. Solid tumours rely on having an extensive network of blood vessels for growth and survival. The key mediator of angiogenesis, vascular endothelial growth factor-A (VEGF-A), is critical for the growth of tumours and their subsequent metastasis and is known to initiate angiogenesis. Bevacizumab is a humanized immunoglobulin G monoclonal antibody that binds to VEGF with high specificity, thereby blocking VEGF-mediated signalling pathways and thus angiogenesis. Clinical trials have shown that bevacizumab is effective in prolonging survival in patients with metastatic colorectal cancer (CRC) when combined with standard chemotherapy. Consequently, bevacizumab has been approved in combination with 5-fluorouracil-based chemotherapy for first-line treatment of patients with metastatic CRC. Bevacizumab is generally well tolerated in most patients and does not exacerbate the adverse events associated with conventional chemotherapy. Bevacizumab-related side effects are generally manageable; however, monitoring for hypertension, gastrointestinal perforation, bleeding, proteinuria and thromboembolism is advised, especially in patients with predisposing factors. In addition to demonstrated survival benefits, the convenient dosing schedule and lack of interactions should ensure the successful integration of this novel agent into clinical practice.
血管生成是指从已有的血管中生成新血管的过程。在胚胎和新生儿发育过程中,以及对于肿瘤细胞而言,它对于正常细胞和组织的生长与发育至关重要。实体瘤的生长和存活依赖于广泛的血管网络。血管生成的关键介质——血管内皮生长因子-A(VEGF-A),对于肿瘤的生长及其后续转移至关重要,并且已知它能启动血管生成。贝伐单抗是一种人源化免疫球蛋白G单克隆抗体,它能高度特异性地结合VEGF,从而阻断VEGF介导的信号通路,进而抑制血管生成。临床试验表明,贝伐单抗与标准化疗联合使用时,可有效延长转移性结直肠癌(CRC)患者的生存期。因此,贝伐单抗已被批准与基于5-氟尿嘧啶的化疗联合用于转移性CRC患者的一线治疗。大多数患者对贝伐单抗的耐受性通常良好,且不会加重与传统化疗相关的不良事件。贝伐单抗相关的副作用通常是可控的;然而,建议对高血压、胃肠道穿孔、出血、蛋白尿和血栓栓塞进行监测,尤其是对于有易感因素的患者。除了已证明的生存获益外,方便的给药方案和无相互作用的特点应能确保这种新型药物成功融入临床实践。