RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF MERIVA (R) AS A CANDIDATE CHEMOPREVENTION AGENT FOR GASTRIC CARCINOGENESIS

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Gastric cancer (GC) is the 4th most common incident cancer and the 2nd leading cause of cancer death worldwide.1 Approximately 990,000 people are diagnosed with GC worldwide, of whom close to 75% die from this disease.2 GC also is responsible for one of the highest cancer burdens, as determined by disability-adjusted life years lost.3 Despite the overall decrease in the incidence of GC since the 1930s, the annual global burden of cancer is projected to double by 2030 to 22.2 million incident cases and 13.1 million deaths, with over two-thirds of the burden in resource-limited nations.4, 5 In the US, the American Cancer Society estimates that in 2015 24,590 new cases of GC will be diagnosed and approximately 10,720 individuals will die from this type of cancer.6 The average risk that a person will develop GC in his/her lifetime is about 1 in 111, with the risk being 2 to 3-fold higher in men than women. However, GC incidence rates vary dramatically across different countries and are higher in less developed countries.2 GC is more common in East Asia, Southern and Eastern Europe, and South and Central America whereas the lowest incidence rates are observed in Africa and North America.7 Although nearly 60% of the new GC cases are diagnosed in Asia,8 significantly better outcomes have been reported among Asian individuals compared to those diagnosed in Western countries.9 Five-year GC survival rates are 40% lower in the US and Europe compared to Japan.10 With the high GC mortality-to-incidence ratio and the lack of routine screening methods available for asymptomatic individuals, the management of GC remains a challenge and warrants further investigations to more fully understand the biologic basis of progression and to develop chemopreventive strategies for individuals at increased risk. Curcumin is a phenolic antioxidant compound derived from the rhizome of the plant Curcuma longa. This bioflavonoid is a potent inhibitor of arachidonic acid metabolism, and blocks both lipoxygenase and cyclooxygenase activity in the intestinal mucosa. Curcumin exerts a variety of additional immunomodulatory and antioxidant effects and is thought to have broad chemopreventive potential through a variety of molecular mechanisms and cellular pathways, as recently reviewed.11 The investigators (Drs. Cruz-Correa & Morgan) from the Mayo Consortium are proposing a chemopreventive trial on a population at risk for gastric cancer (GC) using Meriva (a liposome-encapsulated formulation of curcumin) and placebo. The hypothesis is that curcumin given to individuals with gastric precancerous lesions – multifocal atrophic gastritis (MAG) & intestinal metaplasia (IM) will have a decrease in markers of inflammation including DNA damage, as compared to placebo, after six months of taking the study agent. Meriva® (Curcumin) is a patented formula of curcumin that includes a dietary phenolic with soy lecithin (non-GMO). The curcumin content and the curcuminoid absorption is 27 fold higher when compared to curcumin alone.