Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

Abstract

Preclinical, epidemiologic, and prior clinical trial data suggest that green tea catechins (GTC) may reduce prostate cancer risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E (PolyE), a proprietary mixture of GTCs, containing 400 mg (-)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year prostate cancer rates on the two study arms. No differences in the number of prostate cancer cases were observed: 5 of 49 (PolyE) versus 9 of 48 (placebo), P = 0.25. A secondary endpoint comparing the cumulative rate of prostate cancer plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3 of 26 (PolyE) versus 10 of 25 (placebo), P < 0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared with the placebo arm (5/25). A decrease in serum prostate-specific antigen (PSA) was observed on the PolyE arm [-0.87 ng/mL; 95% confidence intervals (CI), -1.66 to -0.09]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP.

Trial registration: ClinicalTrials.gov NCT00596011.

©2015 American Association for Cancer Research.

Figures

Figure 1

Consort Diagram 1Previously undetected exclusionary medical factors included 13 patients with elevated liver function results, 5 with other lab abnormality, 3 with history of GI disorder, 5 with PSA>10, and 1 taking exclusionary medication. 2Further review of pathology revealed PCa in 2 subjects (ASAP), 1 repeat diagnostic biopsy positive for PCa.(HGPIN) 32 subjects withdrew consent and 11 off study due to AE (4 unrelated, 6 probably related, and 1 possibly related to study) 43 subjects withdrew consent; 7 off study due to AE (5 unrelated and 2 probably related to study)

Figure 2

Change in individual plasma EGCG concentrations at baseline, 6 and 12 months by treatment arm. Most subjects in the placebo arm had non-detectable plasma EGCG concentrations at each time point.