Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid

Gut. 2014 Nov;63(11):1760-8. doi: 10.1136/gutjnl-2013-306445. Epub 2014 Jan 27.


Background: Oral administration of the omega-3 fatty acid eicosapentaenoic acid (EPA), as the free fatty acid (FFA), leads to EPA incorporation into, and reduced growth of, experimental colorectal cancer liver metastases (CRCLM).

Design: We performed a Phase II double-blind, randomised, placebo-controlled trial of EPA-FFA 2 g daily in patients undergoing liver resection surgery for CRCLM. The patients took EPA-FFA (n=43) or placebo (n=45) prior to surgery. The primary end-point was the CRCLM Ki67 proliferation index (PI). Secondary end-points included safety and tolerability of EPA-FFA, tumour fatty acid content and CD31-positive vascularity. We also analysed overall survival (OS) and disease-free survival (DFS).

Results: The median (range) duration of EPA-FFA treatment was 30 (12-65) days. Treatment groups were well matched with no significant difference in disease burden at surgery or preoperative chemotherapy. EPA-FFA treatment was well tolerated with no excess of postoperative complications. Tumour tissue from EPA-FFA-treated patients demonstrated a 40% increase in EPA content (p=0.0008), no difference in Ki67 PI, but reduced vascularity in 'EPA-naïve' individuals (p=0.075). EPA-FFA also demonstrated antiangiogenic activity in vitro. In the first 18 months after CRCLM resection, EPA-FFA-treated individuals obtained OS benefit compared with placebo, although early CRC recurrence rates were similar.

Conclusions: EPA-FFA therapy is safe and well tolerated in patients with advanced CRC undergoing liver surgery. EPA-FFA may have antiangiogenic properties. Remarkably, limited preoperative treatment may provide postoperative OS benefit. Phase III clinical evaluation of prolonged EPA-FFA treatment in CRCLM patients is warranted.

Trial identifier: NCT01070355.

Keywords: Angiogenesis; Colorectal Cancer; Fatty Acid Supplementation; Lipid Mediators; Liver Metastases.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticarcinogenic Agents / therapeutic use*
  • Chromatography, Liquid
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Double-Blind Method
  • Eicosapentaenoic Acid / metabolism
  • Eicosapentaenoic Acid / pharmacology*
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Tandem Mass Spectrometry


  • Anticarcinogenic Agents
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Eicosapentaenoic Acid

Associated data