Oral administration of the omega-3 fatty acid eicosapentaenoic acid (EPA), as the free fatty acid, leads to EPA incorporation into, and reduced growth of, experimental colorectal cancer liver metastases.
Prof Mark Hull and colleagues performed a Phase II double-blind, randomized, placebo-controlled trial of EPA-free fatty acid 2g daily in patients undergoing liver resection surgery for colorectal cancer liver metastases.
The patients took EPA-free fatty acid or placebo prior to surgery.
The team found that primary end-point was the colorectal cancer liver metastases Ki67 proliferation index.
The team's secondary end-points included safety and tolerability of EPA-free fatty acid, tumor fatty acid content and CD31-positive vascularity.
The researchers also analyzed overall survival, and disease-free survival.
|Tumor tissue from EPA-free fatty acid-treated patients demonstrated a 40% increase in EPA content|
The median (range) duration of EPA-free fatty acid treatment was 30 days.
Treatment groups were well matched with no significant difference in disease burden at surgery or preoperative chemotherapy.
The team observed that EPA-free fatty acid treatment was well tolerated with no excess of postoperative complications.
Tumor tissue from EPA-free fatty acid-treated patients demonstrated a 40% increase in EPA content, no difference in Ki67 PI, but reduced vascularity in ‘EPA-naïve’ individuals.
The team noted that EPA-free fatty acid also demonstrated antiangiogenic activity in vitro.
In the first 18 months after colorectal cancer liver metastases resection, EPA-free fatty acid-treated individuals obtained overall survival benefit compared with placebo, although early colorectal cancer recurrence rates were similar.
Prof Mark Hull's team concludes, "EPA-free fatty acid therapy is safe and well tolerated in patients with advanced colorectal cancer undergoing liver surgery."
"EPA-free fatty acid may have antiangiogenic properties."
"Remarkably, limited preoperative treatment may provide postoperative overall survival benefit."
"Phase III clinical evaluation of prolonged EPA-free fatty acid treatment in colorectal cancer liver metastases patients is warranted."