Targeting vascular endothelial growth factor in colorectal cancer.

Berlin JD
Oncology (Williston Park). 2002 16 (8 Suppl 7): 13-5

PMID: 12199627

Recent trials have established the IFL combination (fluorouracil [5-FU], leucovorin, and irinotecan [CPT-11, Camptosar]) as a new standard first-line therapy for patients with metastatic colorectal cancer. Median survival for such patients treated with IFL still ranges from approximately 14 to 18 months, however, underscoring the need for new agents with novel mechanisms of action. Angiogenesis has become an attractive target for anticancer drug development, based on its important roles in tumor growth, invasion, and metastasis. A potent stimulus of angiogenesis is vascular endothelial growth factor (VEGF); two agents developed to inhibit VEGF activity, bevacizumab (Avastin) and SU5416, are in advanced clinical trials. Based on encouraging results in phase I and II trials with bevacizumab, a randomized trial of IFL with or without this monoclonal antibody is under way. Similarly, a randomized trial of 5-FU and leucovorin with or without the tyrosine kinase inhibitor SU5416 has recently completed accrual and results are pending. SU5416 is also being tested in a phase I/II trial combined with IFL. This article briefly reviews preclinical and clinical data leading to the current trials of these two agents in patients with colorectal cancer.

MeSH Terms (24)

Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols Bevacizumab Biomarkers, Tumor Camptothecin Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic Colorectal Neoplasms Disease-Free Survival Endothelial Growth Factors Female Fluorouracil Humans Indoles Irinotecan Leucovorin Male Neovascularization, Pathologic Prognosis Pyrroles Randomized Controlled Trials as Topic Survival Analysis Treatment Outcome

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