Omega-3 Formulation Has Antineoplastic Activity in Patients With Familial Adenomatous Polyposis

Megan Brooks

March 19, 2010

March 19, 2010 — An enteric-coated formulation of the omega-3 free fatty acid form of eicosapentaenoic acid (EPA-FFA; SLA Pharma) showed strong chemopreventive effects in a study of patients with familial adenomatous polyposis (FAP).

Compared with placebo, EPA-FFA treatment for 6 months significantly reduced rectal polyp number and size, with effects "similar in magnitude" to those observed with the selective cyclo-oxygenase-2 inhibitor celecoxib, according to a study published online March 17 in the journal Gut.

Long-term use of the selective cyclo-oxygenase 2 inhibitor celecoxib, which is currently used as an adjunct to endoscopic surveillance in patients with FAP, has significant cardiovascular toxicity, and there is a need for an alternative chemoprevention agent, Mark Hull, MD, PhD, from the Section of Molecular Gastroenterology, Leeds Institute of Molecular Medicine, St. James's University Hospital, United Kingdom, and colleagues note in their report.

Building on positive results with EPA-FFA in a small phase 2 study of patients with a history of sporadic colorectal adenoma, the researchers studied its effects in 55 patients with FAP aged 18 years and older who had previously undergone colectomy with ileorectal anastomosis. The patients were randomly assigned to either the highly purified form of the omega-3 polyunsaturated fatty acid EPA-FFA (2 g daily) or matching placebo for 6 months.

EPA-FFA treatment led to a 2.6-fold increase on average in mucosal EPA levels (P = .018 compared with placebo).

The mean number of polyps at baseline flexible sigmoidoscopy was similar in the 28 patients in the EPA-FFA group and the 27 patients in the placebo group. At 6 months, the mean number of polyps in the same mucosal field decreased 12.4% in the EPA-FFA group (from 4.13 to 3.61) but increased 9.7% in the placebo group (from 4.50 to 5.05).

On intention-to-treat analysis, EPA-FFA for 6 months was associated with a mean 22.4% reduction in polyp number (95% confidence interval [CI], 5.1% - 39.6%; P = .012).

The sum of polyp diameters increased by 17.2% during placebo treatment but decreased by 12.6% during EPA-FFA treatment, representing a 29.8% decrease in the sum of polyp diameters (95% CI, 3.6% - 56.1%; P = .027).

Consistent with the polyp number and size data, global polyp burden worsened during 6 months in the placebo group (−0.34), and there was a modest improvement in the EPA-FFA group (+0.09; difference, 0.42; 95% CI, 0.10 - 0.75; P = .011).

In a telephone interview with Medscape Hematology-Oncology, Raymond DuBois, MD, PhD, provost and executive vice president of M.D. Anderson Cancer Center, Houston, Texas, who was not involved in the study, noted that the efficacy of EPA-FFA was "about the same" as has been shown with celecoxib, and "the advantage would be avoidance of potential cardiovascular side effects."

EPA-FFA was well-tolerated, Dr. Hull and colleagues report, with diarrhea, the most common adverse effect, being reported by a similar number of patients in the EPA-FFA and placebo groups (31.0% and 34.5%, respectively). The frequency of other adverse effects was also similar, except for nausea, which was reported by 9 patients in the EPA-FFA group (31.0%) compared with 3 patients in the placebo group (10.3%). No bleeding episodes were reported during the study.

"It is possible that EPA-FFA may combine [colorectal cancer] chemopreventive efficacy with cardiovascular benefits, which is a particularly attractive therapeutic strategy for middle-to-old age populations relevant to secondary prevention of 'sporadic' colorectal neoplasia," the investigators conclude.

Overall, Dr. DuBois said the results in this study are "believable and what would be expected; however, more [research] is needed to understand the mechanisms better."

The study was supported by SLA Pharma AG, Liestal, Switzerland, which markets EPA-FFA as ALFA. Dr. DuBois has disclosed no relevant financial relationships.

Gut. Published online March 17, 2010.