Targeting Vascular Endothelial Growth Factor in Colorectal Cancer

Colorectal cancer is the second leading cause of cancer death in the United States, with approximately 45,000 deaths and 130,000 newly diagnosed patients per year.[1] Recently, two trials randomized patients to fluorouracil (5-FU)/leucovorin or IFL (5-FU/leucovorin plus irinotecan [CPT-11, Camptosar]) as first-line therapy for metastatic colorectal cancer. The primary end point of both trials was time to tumor progression. One of the trials, conducted in the United States, used IFL at a weekly × 4 schedule for each 6-week treatment cycle, and also had an irinotecan-alone arm.[2] This trial resulted in a higher response rate and longer time to tumor progression for IFL compared with 5-FU/leucovorin, and also a statistically significant survival benefit (14.8 vs 12.6 months, P = .04). The other trial, conducted in Europe, allowed sites to choose one of two infusion schedules (once weekly or every 2 weeks) for the 5-FU/leucovorin regimen.[3] Patients were then randomly assigned to the 5-FU/leucovorin regimen alone or in conjunction with irinotecan. Results of this trial also showed a higher response rate and longer time to tumor progression for IFL compared with 5-FU/leucovorin. A survival benefit was demonstrated for IFL compared with 5-FU/leucovorin as first-line therapy (17.4 vs 14.1 months, respectively; P = .031). However, median survival (14.8 to 17.4 months) obtained with IFL is still limited. New active agents, ideally ones that target intracellular mechanisms or pathways, are still needed.