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

Cockbain, A.J.
; 
Volpato, Milène
; 
Race, Amanda D.
; 
Munarini, A.
; 
Fazio, C.
; 
Belluzzi, A.
; ; 
Toogood, G.J.
; 
Hull, M.A.
Publication Date
2014
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Keywords
Colorectral cancer, Omega-3 polyunsaturated fatty acid, Eicosapentaenoic acid, EPA, Free fatty acid, FFA, Liver metastases
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Peer-Reviewed
Yes
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closedAccess
Accepted for publication
2014-01-03
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Life Sciences Publications
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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-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: ClinicalTrials.gov NCT01070355.
URI
http://hdl.handle.net/10454/10000
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Citation
Cockbain AJ, Volpato M, Race AD et al (2014) Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut. 63(11): 1760-1768.
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Link to Version of Record
https://doi.org/10.1136/gutjnl-2013-306445
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