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Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid
- Source :
- Gut. 63:1760-1768
- Publication Year :
- 2014
- Publisher :
- BMJ, 2014.
-
Abstract
- 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-naive’ 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: ClinicalTrials.gov NCT01070355.
- Subjects :
- Adult
Male
medicine.medical_specialty
Proliferation index
Colorectal cancer
Placebo
complex mixtures
Gastroenterology
Double-Blind Method
Tandem Mass Spectrometry
Internal medicine
medicine
Anticarcinogenic Agents
Humans
health care economics and organizations
Aged
Aged, 80 and over
chemistry.chemical_classification
business.industry
Liver Neoplasms
Fatty acid
Cancer
Middle Aged
medicine.disease
Immunohistochemistry
Eicosapentaenoic acid
Surgery
Platelet Endothelial Cell Adhesion Molecule-1
Eicosapentaenoic Acid
chemistry
Tolerability
Female
lipids (amino acids, peptides, and proteins)
Colorectal Neoplasms
business
Chromatography, Liquid
Polyunsaturated fatty acid
Subjects
Details
- ISSN :
- 14683288, 00175749, and 01070355
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Gut
- Accession number :
- edsair.doi.dedup.....dab5a28bbac1a72c4ccefb8392ae13f3