Can inhibition of angiogenic pathways increase the efficacy of intravenous 5-fluorouracil-based regimens?

First-line irinotecan-containing regimens are toxic and may not be tolerated well by all patient subgroups. Trials evaluating less toxic regimens include a randomized, double-blind, multicenter study (AVF2192g) assessing 5-fluorouracil (5-FU)/leucovorin (LV) with bevacizumab. Patients were randomized to 1 of 2 treatment arms. In arm 1, patients received LV intravenously (I.V.) over 2 hours and 5-FU I.V. over 1 hour every week for 6 weeks of an 8-week cycle, and bevacizumab 5 mg/kg was administered I.V. over 30-90 minutes every 2 weeks. In the second arm, patients received LV and 5-FU as in arm 1, and placebo I.V. over 30-90 minutes every 2 weeks. The primary objective was duration of survival. Eligible patients with untreated metastatic colorectal cancer (CRC) were >or= 65 years of age, had an Eastern Cooperative Oncology Group performance status of 1/2, a serum albumin level