title: Pharmacokinetic and pharmacodynamic evaluation of aflibercept for the treatment of colorectal cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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 ; tmacarulla@vhebron.net.
authors.forename: Enrique
authors.initials: E
authors.lastname: Sanz-Garcia
authors.forename: Tamara
authors.initials: T
authors.lastname: Saurí
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.forename: Teresa
authors.initials: T
authors.lastname: Macarulla
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: VEGF; VEGF-Trap; aflibercept; angiogenesis; metastatic colorectal cancer