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dc.contributor.authorCockbain, A.J.*
dc.contributor.authorVolpato, Milène*
dc.contributor.authorRace, Amanda D.*
dc.contributor.authorMunarini, A.*
dc.contributor.authorFazio, C.*
dc.contributor.authorBelluzzi, A.*
dc.contributor.authorLoadman, Paul M.*
dc.contributor.authorToogood, G.J.*
dc.contributor.authorHull, M.A.*
dc.date.accessioned2016-10-21T09:58:13Z
dc.date.available2016-10-21T09:58:13Z
dc.date.issued2014
dc.identifier.citationCockbain 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.en_US
dc.identifier.urihttp://hdl.handle.net/10454/10000
dc.descriptionNoen_US
dc.description.abstractBackground 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.en_US
dc.description.sponsorshipThe Cancer Research UK Clinical Trials Awards and Advisory Committee approved the Trial. PML and ADR were supported by Department of Health/Cancer Research UK Yorkshire Experimental Cancer Medicine Centre funding. The Trial was adopted by the UKCRN Clinical Trials Portfolio (UKCRN ID 8946) allowing West Yorkshire Comprehensive Local Research Network funding of Pharmacy costs. SLA Pharma AG funded some of the experimental work and provided EPA-FFA and placebo. SLA Pharma AG played no role in the design or execution of the Trial. Laboratory costs were also supported by the Leeds Teaching Hospitals Charitable Foundation (Rays of Hope).en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1136/gutjnl-2013-306445en_US
dc.subjectColorectral cancer; Omega-3 polyunsaturated fatty acid; Eicosapentaenoic acid; EPA; Free fatty acid; FFA; Liver metastasesen_US
dc.titleAnticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic aciden_US
dc.status.refereedYesen_US
dc.date.Accepted2014-01-03
dc.date.application2014-01-27
dc.typeArticleen_US
dc.type.versionNo full-text in the repositoryen_US


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