A Phase 1b Study Evaluating Oral Administration of Freeze-Dried Black Raspberries in Patients with Barrett’s Esophagus.

L. A. Kresty, J. Fromkes, C. Hammond, M. Baird, J. Meile, and G. D. Stoner, The Ohio State University, College of Medicine and Public Health, Columbus, Ohio

Increased fruit and vegetable consumption is associated with decreased risk of a number of cancers, particularly those of epithelial origin. Our laboratory is utilizing two approaches to assess the chemopreventive potential of various berries. The first approach is “food-based” utilizing whole berries delivered in a freeze-dried form; while, the second approach utilizes berry extracts or concentrated fractions derived from whole freeze-dried berries. Dietary administration of freeze-dried black raspberries in the range of 5-10% has significantly inhibited chemically induced oral, esophageal, and colon carcinogenesis in various animal models. Likewise, berry extracts added at 100 µM concentrations to human and rat esophageal cell lines significantly inhibited cell growth. Positive results in preclinical studies utilizing animal models and cell culture experimentation has supported further investigation of berries and berry extracts in high-risk human cohorts, such as patients with existing premalignancies or patients considered to be at risk for cancer recurrence. We are currently conducting a six month chemopreventive pilot study administering 32 or 45 g (female and male, respectively) of freeze-dried black raspberries to patients with Barrett’s esophagus. Barrett’s esophagus represents a change from the normal stratified squamous epithelium to a metaplastic columnar-lined epithelium. Ultimately, Barrett’s importance lies in the fact that it confers a 30-40 fold increased risk for the development of esophageal adenocarcinoma, a malignancy which has increased more rapidly than any other solid tumor during the last three decades. The precise reason for the rapid increase remains to be elucidated, but increasing rates have been linked to long standing acid reflux and obesity. Esophageal cancer is currently the sixth most common cause of cancer deaths among U.S. males and the five year survival rate for those diagnosed with esophageal cancer remains a dismal 14%. These statistics reflect the urgent need for improved treatment and preventive strategies for esophageal cancer. Barrett’s esophagus represents the only recognized precursor lesion to esophageal adenocarcinoma. Thus, these patients represent a population for whom targeted chemoprevention interventions may prove particularly beneficial. The current ongoing phase 1 study seeks to evaluate the ability of freeze-dried black raspberries to modulate tissue, blood and urinary biomarkers associated with oxidative stress, DNA damage and premalignant progression. Details of this study, including factors critical to screening, sampling, and biomarker assessment, will also be discussed.