NO BENEFIT OF ADDING BEVACIZUMAB TO ADJUVANT CHEMOTHERAPY AFTER RESECTION OF HEPATIC METASTASES FROM COLORECTAL CANCER

NEW YORK (Reuters Health) Jan 06 - The addition of bevacizumab to hepatic arterial infusion and systemic chemotherapy does not improve survival in patients who have undergone liver resection for metastases from colorectal cancer.

These findings, from a small phase II trial by researchers at Memorial Sloan-Kettering Cancer Center, New York, were published online on December 28 by the Journal of Clinical Oncology.

"The study cannot provide definitive results because of its size," write Dr. Nancy E. Kemeny and colleagues, but it does suggest that in addition to not lengthening patients' survival, bevacizumab increased biliary toxicity.

Four-year survival following liver resection was 81% in the bevacizumab arm and 85% in the control arm.

The authors note that when the current trial began, no trials using adjuvant bevacizumab to treat colon cancer had been published. Bevacizumab is an antivascular endothelial growth factor A monoclonal antibody first approved in 2004.

Since then, however, a trial of systemic fluorouracil, leucovorin and oxaliplatin with or without bevacizumab in patients with stage II or III colon cancer found no difference in disease-free survival.

Similarly, another trial found no disease-free survival benefit from bevacizumab added to chemotherapy in patients with stage III colon cancer.

The current study involved 73 patients who had colorectal adenocarcinoma with fully resected liver metastases.

Chemotherapy began four to five weeks after surgery. Adjuvant hepatic arterial infusion with fluorodeoxyuridine and dexamethasone took place on day one of a five-week cycle.

On days 15 and 29, patients who had not previously been given oxaliplatin received it (85 mg/m2), along with leucovorin (400 mg/m2), followed by a 48-hour infusion of fluorouracil (2,000 mg/m2). Those who had previously received oxaliplatin were instead given irinotecan (150 mg/m2) with the same doses of leucovorin and fluorouracil.

Participants in the bevacizumab arm received that drug (5 mg/kg) also on days 15 and 29.

The majority of patients in each arm received all six planned cycles of chemotherapy.

The study was terminated early because of signs of biliary toxicity in the bevacizumab arm. Bilirubin levels more than 3 mg/dl and biliary stents were significantly more common among patients in the bevacizumab arm.

The study was supported in part by Genentech, which makes bevacizumab under the trade name Avastin.

J Clin Oncol. Posted online December 28, 2010. Abstract