Targeted therapy for metastatic colorectal cancer: role of aflibercept.

摘要: Worldwide, colorectal cancer (CRC) is the third most commonly diagnosed in male individuals and second female individuals. Survival outcomes are less than optimal for patients with metastatic disease, a 5-year survival 5% to 8% range. The development of new chemotherapeutic agents effective combination regimens (mCRC) has increased median overall (OS) 24- 28-month Because recognition that vascular endothelial growth factors (VEGFs) their receptors primary regulators physiologic pathologic angiogenesis lymphangiogenesis, leading neovascularization tumor growth, targeting angiogenic pathway become focus key therapeutic strategies mCRC. Therapeutic include bevacizumab, an inhibitor VEGF-A, cytotoxic chemotherapy, have resulted improved response rate (RR) However, effects VEGF-A inhibition often temporary, resistance disease progression developing patients. Proposed models intrinsic adaptive resistance, mediated by other VEGF-A. Aflibercept (known as ziv-aflibercept United States; Zaltrap®, Regeneron Pharmaceuticals; sanofi-aventis), novel recombinant fusion protein, factor trap blocks binding VEGF-B, placental factor. Phase I/II clinical trials demonstrated activity mCRC, acceptable safety tolerability. A recent phase III randomized double-blind trial previously treated oxaliplatin reported significant improvement OS, progression-free (PFS), RR aflibercept compared placebo when administered irinotecan fluorouracil. Adverse events were consistent anti-VEGF therapy. Thus represents potential treatment option