Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis

Cancer. 2015 Oct 15;121(20):3649-58. doi: 10.1002/cncr.29534. Epub 2015 Jul 6.


Background: Reports have demonstrated the superior activity of combining both irinotecan and oxaliplatin (FOLFOXIRI) therapy. An option for gaining similar benefits with less toxicity would be the administration of irinotecan through a hepatic artery approach. The aim of this study was to assess the response and adverse event rates for irinotecan drug-eluting beads (DEBIRI) with folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab as a first-line treatment for unresectable colorectal liver metastasis.

Methods: Patients with colorectal liver metastases were randomly assigned to modified FOLFOX (mFOLFOX) and bevacizumab or mFOLFOX6, bevacizumab, and DEBIRI (FOLFOX-DEBIRI). The primary endpoint was the response rate. The secondary endpoints were adverse events, the rate of conversion to resection, and progression-free survival.

Results: The intention-to-treat population comprised 70 patients: 10 patients in the pilot and then 30 patients randomly assigned to the FOLFOX-DEBIRI arm and 30 patients randomly assigned to the FOLFOX/bevacizumab arm. The 2 groups were similar with respect to the extent of liver involvement (30% vs 30%), but a greater percentage of patients in the FOLFOX-DEBIRI arm had an Eastern Cooperative Oncology Group performance status of 1 or 2 (57% vs 31%) and extrahepatic disease (56% vs 32%, P = .02). The median numbers of chemotherapy cycles were similar (10 vs 9), and there were similar rates of grade 3/4 adverse events (54% for the FOLFOX-DEBIRI group vs 46% for the FOLFOX/bevacizumab group). The overall response rate was significantly greater in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm at 2 (78% vs 54%, P = .02), 4 (95% vs 70%, P = .03), and 6 months (76% vs 60%, P = .05). There was significantly more downsizing to resection in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm (35% vs 16%, P = .05), and there was improved median progression-free survival (15.3 vs 7.6 months).

Conclusions: The simultaneous administration of mFOLFOX6 (with or without bevacizumab) and DEBIRI through the hepatic artery (FOLFOX-DEBIRI) is safe and does not cause treatment delays or increase the systemic toxicity of chemotherapy. This strategy leads to improved overall response rates, improved hepatic progression-free survival, and more durable overall progression-free survival in patients downsized to resection.

Keywords: hepatic artery therapy; irinotecan; liver-directed therapy; liver-dominant metastatic colorectal cancer; metastatic colon cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Hepatic Artery / drug effects
  • Humans
  • Irinotecan
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Treatment Outcome


  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Bevacizumab
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol