J Clin Oncol. 2007 Apr 20;25(12):1539-44.
in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4)
for previously treated metastatic colorectal cancer: results from the
Eastern Cooperative Oncology Group Study E3200.
Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB 3rd; Eastern Cooperative Oncology Group Study E3200.
University of Pennsylvania, Philadelphia, PA, USA.
Colorectal cancer is the second leading cause of cancer mortality in
the United States. Antiangiogenic therapy with bevacizumab combined
with chemotherapy improves survival in previously untreated metastatic
colorectal cancer. This study was conducted to determine the effect of
bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based
chemotherapy in patients with previously treated metastatic colorectal
cancer. PATIENTS AND METHODS: Eight hundred twenty-nine metastatic
colorectal cancer patients previously treated with a fluoropyrimidine
and irinotecan were randomly assigned to one of three treatment groups:
oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab;
FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end
point was overall survival, with additional determinations of
progression-free survival, response, and toxicity. RESULTS: The median
duration of survival for the group treated with FOLFOX4 and bevacizumab
was 12.9 months compared with 10.8 months for the group treated with
FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011),
and 10.2 months for those treated with bevacizumab alone. The median
progression-free survival for the group treated with FOLFOX4 in
combination with bevacizumab was 7.3 months, compared with 4.7 months
for the group treated with FOLFOX4 alone (corresponding hazard ratio
for progression = 0.61; P < .0001), and 2.7 months for those treated
with bevacizumab alone. The corresponding overall response rates were
22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with
bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with
hypertension, bleeding, and vomiting. CONCLUSION: The addition of
bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves
survival duration for patients with previously treated metastatic