Phase II randomized, double-blinded, placebo-controlled trial of polyphenon E in patients with prior advanced adenomas or colon cancer

Background. Epidemiologic and preclinical data suggest that green tea catechins may reduce colorectal cancer (CRC) risk. We conducted a phase II study to determine the chemopreventive efficacy and safety of green tea‐derived Polyphenon E (Poly E) in patients at high risk of CRC. The effect of Polyp E treatment on rectal aberrant crypt foci (ACF), putative precursors of colorectal cancers, was studied. Materials & Methods. Among patients with prior advanced adenoma (N=37) or colon cancer (N=2), those with at least 5 rectal ACF at baseline (N=39) were randomized to 6‐months of twice daily (BID) oral Poly E (containing 800 mg of EGCG) or placebo. Chromoendoscopy (using methylene blue) including biopsies, was performed to evaluate and quantify rectal ACF before and after treatment. The primary endpoint was percent reduction in the number of rectal ACF. Results. Baseline patient characteristics were similar between treatment arms (all p>0.41). Of 39 patients, 32 (82%) received 6 months of treatment; 7 discontinued early due to refusal of further treatment (n=6) or an adverse event (AE) (n=1). The total drug received over 6 months did not differ significantly by study arm (p=0.14). Among the 32 patients (15‐ Poly E; 17‐Placebo), the percent change in rectal ACF (baseline vs 6‐month) did not differ significantly between the study arms (p=0.56), and the total ACF burden was similar (p=0.83). Polyp recurrence rates were also similar between arms (p>0.35) at 6 months, and extended follow‐up is ongoing. A secondary objective was drug safety. Poly E treatment was well tolerated; most patients received at least 70% of the prescribed dose [31 (79%)]. Adverse events were similar between the study arms; only 1 patient (placebo arm) had any grade 3 AE. Two patients (1 for each arm) had grade 2+ AEs (PolyE: elevated AST, ALT) and neither were attributed to study treatment. Conclusion. Treatment with Poly E for 6 months did not significantly reduce rectal ACF relative to placebo. PolyE was well tolerated and without significant toxicity at the dose studied.