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Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3502-3508
© 2005 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2005.10.017
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Bevacizumab in Combination With Fluorouracil and Leucovorin: An Active Regimen for First-Line Metastatic Colorectal Cancer

Herbert I. Hurwitz, Louis Fehrenbacher, John D. Hainsworth, William Heim, Jordan Berlin, Eric Holmgren, Julie Hambleton, William F. Novotny, Fairooz Kabbinavar

From the Duke University Medical Center, Durham, NC; Kaiser Permanente Medical Care Program, Northern California; Genentech Inc, South San Francisco; Department of Medicine, University of California at Los Angeles, Los Angeles, CA; The Sarah Cannon Cancer Center, Nashville, TN; Hematology and Cancer Center of Northeastern Pennsylvania, Dunmore, PA; and Division of Medical Oncology, Vanderbilt University Medical Center, Nashville, TN

Address reprint requests to Herbert I. Hurwitz, MD, Department of Medical Oncology and Transplantation, Room 25132, Morris Building, Box 3052, Duke University Medical Center, Durham, NC 27710; e-mail: hurwi004{at}mc.duke.edu

PURPOSE: In a phase III trial, combining bevacizumab (BV)—a recombinant, humanized, monoclonal antibody targeting vascular endothelial growth factor—with irinotecan, bolus fluorouracil (FU), and leucovorin (LV; IFL) increased survival compared with IFL alone in first-line treatment of patients with metastatic colorectal cancer (CRC). Results for the parent study of IFL/BV versus IFL/placebo are reported elsewhere. Here, we describe efficacy and safety results for the third patient cohort in this trial, who received BV combined with FU/LV, and compare them with results for concurrently enrolled patients who received IFL.

METHODS: Patients (N = 923) were randomly assigned to receive IFL/placebo (control), IFL/BV, or FU/LV/BV. Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA) 5 mg/kg was administered intravenously every 2 weeks. Before an interim analysis confirmed acceptable safety for IFL/BV, 313 patients were concurrently randomly assigned to these three arms; after this analysis, the FU/LV/BV arm was discontinued.

RESULTS: Median overall survivals were 18.3 and 15.1 months with FU/LV/BV (n = 110) and IFL/placebo (n = 100), respectively. Median progression-free survivals were 8.8 and 6.8 months, respectively. Overall response rates were 40.0% and 37.0%, and median response durations were 8.5 and 7.2 months, respectively. Adverse events consistent with those expected from FU/leucovorin- or IFL-based regimens were seen, as were modest increases in hypertension and bleeding in the bevacizumab arm, which were generally easily managed.

CONCLUSION: The FU/LV/BV regimen seems as effective as IFL and has an acceptable safety profile. FU/LV/BV is an active alternative treatment regimen for patients with previously untreated metastatic CRC.

H.I.H. was supported in part by career development grant No. K23 CA085582–04 from the National Cancer Institute, National Institutes of Health, Bethesda, MD.

Authors' disclosures of potential conflicts of interest are found at the end of this article.


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