摘要
血管增生是在包括非小细胞型肺癌(NSCLC)的肿瘤发展与转移中最重要现象之一。血管增生的一个主要作用是通过血管内皮细胞生长因子(VEGF)和它的信号通路来实现的。Ramucirumab是能与细胞外血管内皮细胞受体-2 (VEGFR-2)高选择性与特异性结合的,并能阻碍VEGFR-2与VEGF配体联系的人体全免疫球蛋白G1单克隆抗体,因此,它能抑制它们(VEGFR-2, VEGF)的信号通路和间接内皮增生和迁移。最近一个被称为REVEL的随机临床三期实验阐述了ramucirumab结合docetaxel作为晚期非小细胞型肺癌的二线治疗的效能,使得FDA与EMA通过了这次临床试验。在这次试验中,经过基于铂的一线化学治疗的晚期NSCLC患者被给予了ramucirumab+docetaxel或者安慰剂+docetaxel。超过1250名患者接受了治疗,并且随机给予ramucirmab+docetaxel治疗的比随机给予化学疗法的患者表现出的中位生存期明显增长。Ramucirmab是第一种被批准用于治疗鳞状和非鳞状NSCLC的抗血管增生药剂。事实上,它与鳞状组织学上呼吸性出血风险的增长无联系,甚至在两种组织学类型中都表现出了效用。在晚期NSCLC的二线治疗中已被明确的Ramucirumab的作用需要进一步的被阐明,并且最近它在晚期NSCLC一线治疗中的作用正在探索中。
关键词: 血管增生,血管内皮细胞生长因子,血管内皮细胞生长因子受体-2,ramucirumab,晚期非小细胞型肺癌,二线治疗
Current Medicinal Chemistry
Title:The Role of the Antiangiogenetic Ramucirumab in the Treatment of Advanced Non Small Cell Lung Cancer
Volume: 24 Issue: 1
Author(s): Paolo Maione, Assunta Sgambato, Francesca Casaluce, Paola Claudia Sacco, Giuseppe Santabarbara, Antonio Rossi, Cesare Gridelli.
Affiliation:
关键词: 血管增生,血管内皮细胞生长因子,血管内皮细胞生长因子受体-2,ramucirumab,晚期非小细胞型肺癌,二线治疗
摘要: Angiogenesis is one of the most important phenomena sustaining tumor development and metastatization, including for non small cell lung cancer (NSCLC). A dominant role in angiogenesis is played by the vascular endothelial growth factor (VEGF) and its signaling pathway. Ramucirumab, is a fully human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of the VEGF receptor-2 (VEGFR-2) with high specificity and affinity blocking the interaction of VEGFR-2 and VEGF ligands, thus inhibiting their signaling pathways and the consequential endothelial proliferation and migration. A recent phase III randomized trial named REVEL, demonstrated the efficacy of ramucirumab in combination with docetaxel as second line treatment of advanced NSCLC, leading to its FDA and EMA approval in this clinical setting. In the REVEL trial advanced NSCLC patients whose disease had progressed after first line platinum-based chemotherapy, were administered ramucirumab plus docetaxel or placebo plus docetaxel. More than 1,250 patients were treated and patients randomized to the treatment with ramucirumab plus docetaxel showed a significant longer median overall survival compared to those randomized to chemotherapy only. Ramucirumab is the first antiangiogenetic agent approved in the treatment both of squamous and non squamous NSCLC. In fact, it is not associated with increased risk of respiratory bleeding in the squamous histology, and also has demonstrated efficacy in both histology types. The role of ramucirumab, already cleared in the second-line treatment of advanced NSCLC, needs to be clarified further and is currently being explored also in the first-line treatment of advanced NSCLC.
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Paolo Maione, Assunta Sgambato, Francesca Casaluce, Paola Claudia Sacco, Giuseppe Santabarbara, Antonio Rossi, Cesare Gridelli. , The Role of the Antiangiogenetic Ramucirumab in the Treatment of Advanced Non Small Cell Lung Cancer, Current Medicinal Chemistry 2017; 24 (1) . https://dx.doi.org/10.2174/0929867324666161118125103
DOI https://dx.doi.org/10.2174/0929867324666161118125103 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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