Rossi Antonio, Latiano Tiziana Pia, Parente Paola, Chiarazzo Cinzia, Limosani Filomena, Di Maggio Gabriele, Maiello Evaristo
a Oncology Unit , IRCCS Casa Sollievo della Sofferenza Hospital , San Giovanni Rotondo , Italy.
b Pathology Unit , IRCCS Casa Sollievo della Sofferenza Hospital , San Giovanni Rotondo , Italy.
Expert Opin Pharmacother. 2017 Aug;18(11):1153-1162. doi: 10.1080/14656566.2017.1346086. Epub 2017 Jul 6.
Angiogenesis leads to the growth, progression, and metastases of a variety of solid tumors, including metastatic colorectal cancer (mCRC), involving particularly the family of vascular endothelial growth factors (VEGF) and their receptors (VEGFR). Several anti-angiogenic inhibitors are already registered for mCRC therapy: bevacizumab, aflibercept, ramucirumab, regorafenib. Nintedanib is a new triple angiokinase oral inhibitor that potently blocks the proangiogenic pathways mediated by VEGFR, platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). Areas covered: The current state-of-the-art of anti-angiogenic inhibitors employed in the treatment mCRC patients, and in particular the role of nintedanib in this setting, is reviewed and discussed here. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken. Expert opinion: In first-line therapy, a phase II randomized trial showed that nintedanib plus chemotherapy was not inferior to the bevacizumab-based regimen. In heavily pretreated mCRC patients nintedanib improved some outcomes. During the natural history of mCRC resistances to anti-angiogenic therapies can set in and in this context, nintedanib, due to its triple inhibition, might play a role in compensatory angiogenesis overcoming the resistance developed due to VEGF directed therapy.
血管生成会导致包括转移性结直肠癌（mCRC）在内的多种实体瘤生长、进展和转移，这一过程尤其涉及血管内皮生长因子（VEGF）家族及其受体（VEGFR）。几种抗血管生成抑制剂已被注册用于mCRC治疗：贝伐单抗、阿柏西普、雷莫西尤单抗、瑞戈非尼。尼达尼布是一种新型口服三联血管激酶抑制剂，可有效阻断由VEGFR、血小板衍生生长因子受体（PDGFR）和成纤维细胞生长因子受体（FGFR）介导的促血管生成途径。涵盖领域：本文对用于治疗mCRC患者的抗血管生成抑制剂的当前技术水平，特别是尼达尼布在这种情况下的作用进行了综述和讨论。使用聚焦的综述问题对书目数据库中的同行评审研究文献和主要会议进行了结构化检索。专家意见：在一线治疗中，一项II期随机试验表明，尼达尼布联合化疗不劣于基于贝伐单抗的方案。在经过大量预处理的mCRC患者中，尼达尼布改善了一些预后。在mCRC的自然病程中，可能会出现对抗血管生成疗法的耐药性，在这种情况下，由于尼达尼布具有三联抑制作用，它可能在代偿性血管生成中发挥作用，克服因VEGF定向治疗产生的耐药性。
