title: Ziv-aflibercept: a novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer.
abstract: OBJECTIVE
  The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of ziv-aflibercept in combination therapy for metastatic colorectal cancer (mCRC) are reviewed.
  
  
  CONCLUSIONS
  Ziv-aflibercept (Zaltrap, Regeneron Pharmaceuticals and sanofi-aventis) is a novel recombinant fusion protein that targets the angiogenesis signaling pathway of tumor cells by blocking vascular endothelial growth factor (VEGF) receptors that play a key role in tumor growth and metastasis; it is a more potent VEGF blocker than bevacizumab. Ziv-aflibercept is approved by the Food and Drug Administration for use in combination with fluorouracil, irinotecan, and leucovorin (the FOLFIRI regimen) for second-line treatment of patients with mCRC who have disease progression during first-line oxaliplatin-based chemotherapy. A Phase III trial demonstrated that relative to FOLFIRI therapy alone, the use of ziv-aflibercept was associated with significantly improved patient response, overall survival, and progression-free survival in patients with good performance status at baseline, including some who had received prior bevacizumab therapy. The most common grade 3 or 4 adverse effects associated with ziv-aflibercept use in clinical studies were neutropenia, hypertension, and diarrhea; the U.S. product labeling warns of potential hemorrhage and other treatment-related risks.
  
  
  CONCLUSIONS
  Current clinical data are insufficient to directly compare ziv-aflibercept and bevacizumab when used with standard combination chemotherapy as first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently limited to the second-line setting in combination with irinotecan-based regimens in mCRC patients who have not received irinotecan previously. The role of ziv-aflibercept in chemotherapy for other tumor types is yet to be determined.
authors.affiliation: Clement Chung, Pharm.D., BCOP, BCPS, is Oncology Clinical Pharmacist, Lyndon B. Johnson General Hospital, Harris Health System, Houston, TX. Nisha Pherwani, Pharm.D., BCOP, is Clinical Director, Oncology, Cardinal Health Pharmacy Solutions, Houston, TX 77077.
authors.forename: Clement
authors.initials: C
authors.lastname: Chung
authors.forename: Nisha
authors.initials: N
authors.lastname: Pherwani
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor