Combining anti-VEGF approaches with oxaliplatin in advanced colorectal cancer.
Angiogenesis, the formation of blood vessels, is a vital process in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a potential target for antiangiogenic therapy because its overexpression has been associated with tumor vascularity, poor prognosis, and aggressive disease in many malignancies, including colorectal cancer (CRC). Bevacizumab is a recombinant humanized monoclonal antibody against VEGF. It is the first angiogenesis inhibitor to show significant activity in patients and, when combined with chemotherapy, leads to a significant survival benefit in CRC. This monoclonal antibody has been approved for first-line therapy in combination with intravenous 5-fluorouracil-containing regimens in patients with metastatic CRC. Vatalanib (PTK787/ZK222584) is an oral antiangiogenic tyrosine kinase inhibitor of the VEGF receptor. Currently, it is being evaluated in combination with FOLFOX (5-fluorouracil/leucovorin/oxaliplatin) in metastatic CRC. This article reviews the process of angiogenesis and the successful translation of antiangiogenic agents into the clinic. Specifically, studies evaluating VEGF-targeted agents in combination with oxaliplatin-containing regimens in CRC are discussed.
The University of North Carolina at Chapel Hill, NC 27599-7305, USA.
Shannon K
SK
Penland
Richard M
RM
Goldberg
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010793:Phthalazines / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D010793:Phthalazines; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; C431073:oxiplatin; D000068258:Bevacizumab; C404768:vatalanib