Bevacizumab in association with de Gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial.

BACKGROUND: The aim of the current study was the investigation of the value of bevacizumab+5-fluorouracil(5-FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options. METHODS: The authors included 48 heavily pretreated patients (colon:rectum, 33:15; men:women, 23:25; median age, 63 years; range, 27-79 years) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy, an irinotecan-based second-line regimen, and a third-line treatment with cetuximab plus weekly irinotecan. Bevacizumab was given at a dose of 5 mg/kg. 5-FU/folinic acid was administered according to the de Gramont schedule. RESULTS: The response rate was 6.25%, and 30.4% of patients demonstrated stable disease as the best response. The median time to disease progression was 3.5 months (95% confidence interval [95% CI], 2.3-6.9 months), and the median survival time was 7.7 months (95% CI, 3.9-11.9 months). The most common grade 3 to 4 side toxicities (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) were: diarrhea (20.8%), fatigue (14.5%), and stomatitis (12.5%). Grade 3 to 4 hemorrhage occurred in 8 patients (16.6%), including 4 cases of bleeding in the gastrointestinal tract. Other relatively common adverse events such as hypertension, thrombosis, and bowel perforation were reported in 50%, 18.7%, and 4.16%, of patients respectively. CONCLUSIONS: The data from the current study suggest a modest but significant clinical benefit of bevacizumab+de Gramont schedule in heavily pretreated colorectal cancer patients. Copyright (c) 2009 American Cancer Society.