ArticleBMJ open2023
Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol.
Article in BMJ open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03428477 (A Randomised Placebo-controlled Phase III Trial of the Effect of the Omega-3 Fatty Acid Eicosapentaenoic Acid), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomised Placebo-controlled Phase III Trial of the Effect of the Omega-3 Fatty Acid Eicosapentaenoic Acid (EPA) on Colorectal Cancer Recurrence and Survival After Surgery for Resectable Liver Metastases
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.
- Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals.Circulation. Arrhythmia and electrophysiology · 2026Pooled it
- Fatty Acids in Cancer Therapy: Chemical Conjugates, Nanocarriers, and Therapeutic Opportunities.Molecules (Basel, Switzerland) · 2026Review
- Omega-3 fatty acid DHA induces ferroptosis in colorectal cancer patient-derived organoids and drug-tolerant cells.Cell death & disease · 2026Article
- FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages.Cell reports · 2026Article
- Ovarian Tumor FAK Inhibition Releases Omega-3 Fatty Acids Stimulating GATA6 Peritoneal Macrophage CXCL13 Production Enhancing Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Myeloid‑derived suppressor cells: Key immunosuppressive regulators and therapeutic targets in colorectal cancer (Review).International journal of oncology · 2024Review
- Harnessing Oxylipins and Inflammation Modulation for Prevention and Treatment of Colorectal Cancer.International journal of molecular sciences · 2024Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 2 countries.
Funding
Abstract
introductionThere remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. METHODS AND ANALYSIS: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6 monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. ETHICS AND DISSEMINATION: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. TRIAL REGISTRATION NUMBER: NCT03428477.
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Registered trials
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