Sanz-Garcia Enrique, Saurí Tamara, Tabernero Josep, Macarulla Teresa
Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Department of Medical Oncology , P. Vall d'Hebron 119-129, 08035 Barcelona , Spain +34 93 274 6085 ; +34 93 274 6059 ;
Expert Opin Drug Metab Toxicol. 2015 Jun;11(6):995-1004. doi: 10.1517/17425255.2015.1041920.
Colorectal cancer (CRC) is currently one of the most lethal and prevalent tumors worldwide. Prognosis in the metastatic setting remains poor despite therapeutic advances. In addition to chemotherapy, new drugs have recently been developed targeting signaling pathways involved in tumor growth, differentiation and angiogenesis. Aflibercept , a recombinant protein derived from VEGF receptors 1 and 2, also targets this angiogenesis pathway but via a different mechanism, acting as VEGF decoy, thus blocking other VEGFs.
A comprehensive review of preclinical studies with aflibercept in cell lines and xenografts of different tumor types is presented. Aflibercept safety, pharmacokinetics and pharmacodynamics data from Phase I studies in solid tumor patients are discussed. Implications of Phase II studies and the pivotal Phase III VELOUR trial of second-line treatment in metastatic CRC (mCRC) patients evaluating aflibercept alone or combined with chemotherapy are also described.
In this challenging field, aflibercept offers a good option for oxaliplatin-refractory mCRC patients when combined with irinotecan and 5-fluorouracil irrespective of prior anti-angiogenic treatment. Therapeutic management may be further advanced by characterization of patients with predictive biomarkers and molecular profiles to improve benefit with this treatment.
结直肠癌（CRC）是目前全球最致命且最常见的肿瘤之一。尽管治疗取得了进展，但转移性结直肠癌的预后仍然很差。除了化疗之外，最近还开发了针对肿瘤生长、分化和血管生成相关信号通路的新药。阿柏西普是一种源自血管内皮生长因子（VEGF）受体1和2的重组蛋白，它也靶向这一血管生成通路，但通过不同的机制，作为VEGF诱饵，从而阻断其他VEGF。
本文全面综述了阿柏西普在不同肿瘤类型的细胞系和异种移植模型中的临床前研究。讨论了阿柏西普在实体瘤患者I期研究中的安全性、药代动力学和药效学数据。还描述了II期研究的意义以及评估阿柏西普单药或联合化疗用于转移性结直肠癌（mCRC）患者二线治疗的关键III期VELOUR试验。
在这个具有挑战性的领域，对于奥沙利铂难治性mCRC患者，无论之前是否接受过抗血管生成治疗，阿柏西普与伊立替康和5-氟尿嘧啶联合使用都是一个不错的选择。通过对具有预测性生物标志物和分子特征的患者进行特征分析，以提高这种治疗的获益，可能会进一步推进治疗管理。
