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

Abstract

Preclinical, epidemiological and prior clinical trial data suggest that green tea catechins (GTCs) may reduce prostate cancer (PCa) 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 PCa rates on the two study arms. No differences in the number of PCa cases were observed: 5/49 (PolyE) versus 9/48 (placebo), P=0.25. A secondary endpoint comparing the cumulative rate of PCa plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3/26 (PolyE) versus 10/25 (placebo), P<0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared to the placebo arm (5/25). A decrease in serum prostate specific antigen (PSA) was observed on the PolyE arm [−0.87 ng/ml (95%CI: −1.66, −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 PCa in men with baseline HGPIN or ASAP.

Green Tea and Its Extracts in Cancer Prevention and Treatment

“…This study found a lower rise in PSA in the intervention group, as did another study supplementing Polyphenon E instead of GT [200]. In a similarly designed study comparing EGCG extract versus placebo, a significant decrease was obtained only for the combined endpoint "carcinoma plus atypical small acinar proliferations" but not for prostate cancer alone [201]. Contrary to these results, Gontero et al [202] reported an increase in prostate cancer incidence in patients with high grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferations (ASAP), after supplementing the diet with selenium, lycopene and GTE.…”

“…They argue that pharmacology data for neutraceuticals like Polyphenon E and food supplements like GT should be included in any study protocol, as well as for extending these studies to realistic clinical time scenarios relevant for tumor progression (i.e., 5 to 20 years observation). A preliminary evaluation for Polyphenon E versus placebo after one year follow up found no effect [201].…”

Therapeutic effects of EGCG: a patent review

“…Nevertheless few studies on the chemopreventive role of EGCG have yielded inconsistent results. A study performed by Kumar et al showed that daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline highgrade prostatic intraepithelial neoplasia or atypical small acinar proliferation [20]. Most of the clinical trials have certain limitations i.e., short duration and low participation which need to be considered before pronouncing the drug's efficacy or toxicity.…”

“…However, certain studies have also yielded inconsistent results. Another study on prostate intraepithelial neoplasia patients, showed that daily intake of EGCG for a year was well tolerated but did not reduce the likelihood of prostate cancer in men [20]. Individual metabolic differences Expert Opinion on Therapeutic Patents result in differential response; duration and cost associated with clinical trials, limit the use of EGCG for treating diseases and hence call for the need of personalized medicine.…”

Dietary supplements and prostate cancer prevention

“…19 However, the recently published results of an American trial, randomising 97 men with precancerous prostatic lesions to receive polyphenon E (green tea extract) or placebo, revealed no significant difference in prostate cancer incidence. 20 Although not proven dangerous, lycopene and polyphenol have not been proven useful and their use should not be encouraged. …”