Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer.
[I suppose most of us were surprised at the reported success of Avastin to more than meet its endpoint in the colorectal cancer trial that is to be reported at ASCO. If we had seen the following abstract, we might have been less so. Curiously, the low dose bevacizumab arm seems to have given "better" results than the high dose arm.
Erik]
J Clin Oncol 2003 Jan 1;21(1):60-5 (ISSN: 0732-183X)
Kabbinavar F; Hurwitz HI; Fehrenbacher L; Meropol NJ; Novotny WF; Lieberman G; Griffing S; Bergsland E
Division of Hematology-Oncology, University of California Los Angeles, School of Medicine, 90095, USA. fkabbina@mednet.ucla.edu.
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. |
