Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer.

Abstract

PURPOSE:

This phase II trial investigated the safety and efficacy of two doses of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, plus fluorouracil (FU)/leucovorin (LV) versus FU/LV alone in patients with metastatic colorectal cancer.

PATIENTS AND METHODS:

One hundred four previously untreated patients with measurable metastatic colorectal cancer were randomly assigned to one of the following three treatment groups: 36 to FU (500 mg/m(2))/LV (500 mg/m(2)) alone, 35 to FU/LV + low-dose bevacizumab (5 mg/kg every 2 weeks), and 33 to FU/LV + high-dose bevacizumab (10 mg/kg every 2 weeks). FU/LV was given weekly for the first 6 weeks of each 8-week cycle.

RESULTS:

Compared with the FU/LV control arm, treatment with bevacizumab (at both dose levels) plus FU/LV resulted in higher response rates (control arm, 17%, 95% confidence interval [CI], 7% to 34%; low-dose arm, 40%, 95% CI, 24% to 58%; high-dose arm, 24%, 95% CI, 12% to 43%), longer median time to disease progression (control arm, 5.2 months, 95% CI, 3.5 to 5.6 months; low-dose arm, 9.0 months, 95% CI, 5.8 to 10.9 months; high-dose arm, 7.2 months, 95% CI, 3.8 to 9.2 months), and longer median survival (control arm, 13.8 months; 95% CI, 9.1 to 23.0 months; low-dose arm, 21.5 months, 95% CI, 17.3 to undetermined; high-dose arm, 16.1 months; 95% CI, 11.0 to 20.7 months). After cross-over, two of 22 patients had a partial response to bevacizumab alone. Thrombosis was the most significant adverse event and was fatal in one patient. Hypertension, proteinuria, and epistaxis were other potential safety concerns.

CONCLUSION:

The encouraging results of this randomized trial support further study of bevacizumab 5 mg/kg plus chemotherapy as first-line therapy for metastatic colorectal cancer.

• Authors: Fairooz Kabbinavar, Herbert I Hurwitz, Louis Fehrenbacher, Neal J Meropol, William F Novotny, Grazyna Lieberman, Susan Griffing, Emily Bergsland
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 21 Issue 1 Pg. 60-5 (Jan 01 2003) ISSN: 0732-183X [Print] United States
• PMID: 12506171 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Leucovorin
• Fluorouracil

Topics

• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects, pharmacology)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Colorectal Neoplasms (drug therapy, mortality)
• Cross-Over Studies
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Female
• Fluorouracil (administration & dosage)
• Humans
• Leucovorin (administration & dosage)
• Male
• Proportional Hazards Models
• Survival Rate