Ziv-aflibercept

Compound Name:Ziv-afliberceptMolecular Target:VEGF, PIGRMolecular Structure:Fusion protein: IgG Fc, and ligand binding domains of VEGFR-1 and VEGFR-2Licensed Indication:Metastatic colorectal cancerManufacturer and/or Distributor:Regeneron/ Sanofi-AventisInitial FDA Approval2012SummaryZiv-aflibercept is a fusion protein construct consisting of the Fc portion of human IgG linked to the ligand binding domains of the VEGRF-1 and VEGRF-2 receptors. It binds with high affinity to (vascular endothelial growth factor) VEGF-A, VEGF-B, (placental growth factor) PlGF-1 and PlGF-2, and inhibits neovascularization and vascular permeability. It thus exerts an anti-tumor effect. It is the same medicine as aflibercept (Eylea®), which is marketed for treatment of macular degeneration and macular edema following central retinal vein occlusion. Ziv-aflibercept was approved for the treatment of metastatic colorectal cancer that has failed treatment with an oxaliplatin-containing regimen. It is indicated for use in conjunction with 5-fluorouracil, leucovorin, and irinotecan (FOLFORI). In a single phase III trial comparing regimens of FOLFORI with ziv-aflibercept or with placebo, the ziv-aflibercept group showed improved median overal survival and median progression-free survival. The major safety concerns are gastrointestingal hemorrhage, fistula formation or perforation, hypertension, arterial thromboses, proteinuria, neutropenia, severe diarrhea, reversible posterior leukoencephalopathy, and impaired wound healing.References

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1. Ciombor K, Berlin J, Chan E. Aflibercept. Clinical cancer research : an official journal of the American Association for Cancer Research. 2013;19(8):1920-1925.
http://dx.doi.org/10.1158/1078-0432.CCR-12-2911

2. Clarke J, Hurwitz H. Ziv-aflibercept: binding to more than VEGF-A--does more matter? Nature reviews Clinical oncology. 2013;10(1):10-11.
http://dx.doi.org/10.1038/nrclinonc.2012.197

3. Evoy K, Abel S. Aflibercept: newly approved for the treatment of macular edema following central retinal vein occlusion. The Annals of pharmacotherapy. 2013;47(6):819-827.
http://dx.doi.org/10.1345/aph.1R705

4. Ohr M, Kaiser P. Aflibercept in wet age-related macular degeneration: a perspective review. Therapeutic advances in chronic disease. 2012;3(4):153-161.
http://dx.doi.org/10.1177/2040622312446007

5. Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012 Oct 1;30(28):3499-3506.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22949147

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