Division of Medical Oncology, "S.G. Moscati" Hospital, Avellino, Italy.
Curr Cancer Drug Targets. 2012 Mar;12(3):289-99. doi: 10.2174/156800912799277476.
Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85% of all new lung cancer diagnosis. The majority of people with NSCLC are unsuitable for surgery since most patients have metastatic disease at diagnosis. About 60% of brain metastases arise from lung cancer. Therapeutic approaches to brain metastases include surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery, chemotherapy and new biologic agents. Angiogenesis is essential for the development and progression of cancer, and vascular endothelial growth factor (VEGF) is a critical mediator of tumour angiogenesis. One of the targeted approaches most widely studied in the treatment of NSCLC is the inhibition of angiogenesis. Bevacizumab, an anti-VEGF recombinant humanized monoclonal antibody, is the first targeted agent which, when combined with chemotherapy, has shown superior efficacy versus chemotherapy alone as first-line treatment of advanced non-squamous NSCLC patients. Patients with central nervous system (CNS) metastases have initially been excluded from bevacizumab trials for the risk of cerebral haemorrhage as a result of the treatment. Nevertheless, the available data suggest an equal risk of intracranial bleeding in patients with CNS metastases treated with or without bevacizumab therapy. Several other anti-angiogenetic drugs are being investigated in the treatment of advanced NSCLC patients, but results of their activity specifically in CNS metastases are still lacking. This review will focus on the potential role of bevacizumab and other anti-angiogenetic agents in the treatment of brain metastases from NSCLC.
肺癌是全球癌症相关死亡的主要原因，非小细胞肺癌（NSCLC）约占所有新发肺癌诊断的 85%。由于大多数患者在诊断时已患有转移性疾病，大多数 NSCLC 患者不适合手术。约 60%的脑转移来自肺癌。脑转移的治疗方法包括手术、全脑放疗（WBRT）、立体定向放射外科、化疗和新的生物制剂。血管生成对于癌症的发展和进展至关重要，血管内皮生长因子（VEGF）是肿瘤血管生成的关键介质。在 NSCLC 治疗中研究最广泛的靶向方法之一是抑制血管生成。贝伐单抗是一种抗 VEGF 的重组人源化单克隆抗体，是第一种靶向药物，与化疗联合使用时，在晚期非鳞状 NSCLC 患者的一线治疗中优于单独化疗。由于治疗导致脑出血的风险，中枢神经系统（CNS）转移患者最初被排除在贝伐单抗试验之外。然而，现有数据表明，在接受或不接受贝伐单抗治疗的 CNS 转移患者中，颅内出血的风险相同。其他几种抗血管生成药物也在晚期 NSCLC 患者的治疗中进行了研究，但它们在 CNS 转移中的活性的结果仍然缺乏。这篇综述将重点介绍贝伐单抗和其他抗血管生成药物在治疗 NSCLC 脑转移中的潜在作用。
