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

Cancer. 2009 Oct 15;115(20):4849-56. doi: 10.1002/cncr.24540.

Abstract

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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm*
  • Female
  • Fluorouracil / administration & dosage*
  • Humans
  • Leucovorin / administration & dosage*
  • Male
  • Middle Aged
  • Retreatment

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Cetuximab
  • Leucovorin
  • Fluorouracil