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


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.


CONCLUSIONS
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.
Kabbinavar
Fairooz
F
Division of Hematology-Oncology, University of California Los Angeles, School of Medicine, 90095, USA. fkabbina@mednet.ucla.edu
Hurwitz
Herbert I
HI
Fehrenbacher
Louis
L
Meropol
Neal J
NJ
Novotny
William F
WF
Lieberman
Grazyna
G
Griffing
Susan
S
Bergsland
Emily
E
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D016016:Proportional Hazards Models; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil