Bevacizumab plus FOLFIRI-3 in chemotherapy-refractory patients with metastatic colorectal cancer in the era of biotherapies

Invest New Drugs. 2012 Apr;30(2):758-64. doi: 10.1007/s10637-010-9575-3. Epub 2010 Nov 6.

Abstract

Background: The optimal chemotherapeutic regimen suitable for metastatic colorectal cancer (mCRC) patients previously treated with 5-fluorouracil (5FU), oxaliplatin, irinotecan and biotherapies remains an unresolved issue. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI-3 in mCRC after failure of prior chemotherapy including fluoropyrimidine, irinotecan and oxaliplatin.

Methods: Patients were treated with bevacizumab in combination with FOLFIRI-3 every 14 days. The association between treatment efficacy and visceral fat area as measured by CT scan or Carcinoembryonic Antigen (CEA) change after 2 months was also studied.

Results: Forty-nine consecutive patients were treated. Four hundred and twenty four cycles of chemotherapy were delivered. Median follow-up was 11 months. Eleven patients (22.4%) had an objective partial response and 26 (53.1%) were stabilized. Median progression-free survival (PFS) and overall survival (OS) were 7 and 13 months respectively. Four grade 4 adverse events occurred (1 digestive perforation, 1 rectal ulcer, 1 pulmonary embolism, and 1 febrile aplasia) but no toxic death was observed. Grade 3 adverse events occurred in 18 patients (38%) including asthenia in 15 patients (30%), nausea and vomiting in 4 patients (8%), diarrhea in 11 patients (22%), anemia in 4 patients (8%), neutropenia in 10 patients (20%) and thrombopenia in 4 patients (8%). Visceral Fat area was significantly lower in responder patients. CEA change at 2 months predicted improved overall survival.

Conclusion: This study suggests that bevacizumab combined with FOLFIRI3 may be active in mCRC patients after failure of all classical lines of chemotherapy.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carcinoembryonic Antigen / blood
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm*
  • Female
  • Fluorouracil / administration & dosage
  • France
  • Humans
  • Infusions, Intravenous
  • Intra-Abdominal Fat / diagnostic imaging
  • Irinotecan
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Failure

Substances

  • Antibodies, Monoclonal, Humanized
  • Carcinoembryonic Antigen
  • Bevacizumab
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Camptothecin