title: Evaluation of aflibercept in the treatment of metastatic colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer (CRC) is currently the third most common cancer worldwide, with up to 1 million new cases diagnosed each year. Despite improvements in clinical outcomes of patients with this tumor over the past decades, prognosis remains poor with a 5-year survival rate of < 10%. The currently available systemic chemotherapeutic options for patients with colon cancer consist essentially of fluoropyrimidine-based regimens, alone or in combination with oxaliplatin or irinotecan. The addition of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) bevacizumab to the above mentioned first- or second-line chemotherapies has demonstrated an improvement in overall survival and a delay in disease progression. Aflibercept is a recombinant protein from the domain 2 of the VEGF receptor-2 attached to the Fc portion of IgG1. In preclinical studies, aflibercept has demonstrated a more favorable pharmacokinetic profile. Aflibercept has been evaluated in a Phase III study in combination with irinotecan-based chemotherapy in patients with metastatic CRC refractory to oxaliplatin-based chemotherapy. The results of the VELOUR study showed that the addition of aflibercept produced an advantage in both progression-free and overall survival.
  
  
  METHODS
  In this review article, we will look over the preclinical and clinical development of aflibercept.
  
  
  CONCLUSIONS
  In our opinion research is moving forward on a good path; we have seen the recent approval of aflibercept, and in the following years we might have newer standard treatment options among the latest compounds under development.
authors.affiliation: Vall d'Hebron University Hospital , Barcelona , Spain tmacarulla@vhebron.net.
authors.forename: Teresa
authors.initials: T
authors.lastname: Macarulla
authors.forename: Tamara
authors.initials: T
authors.lastname: Sauri
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: VEGF; aflibercept; angiogenesis; colorectal cancer