Chemoprevention trial of green tea polyphenols in high-risk population of liver cancer in southern Guangxi, China

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Green tea polyphenols (GTP) are highly effective chemopreventive agents in inhibition of a variety of carcinogen-induced tumorigenesis in in vitro bioassays and in vivo animal models for different target organ sites, including aflatoxin-induced liver tumors. On the basis of results of our phase II study, a randomized, double blinded, and placebo controlled chemoprevention trial has been carried out in residents of southern Guangxi, PRC since fall 1999. The study had screened 6,681 blood samples for hepatitis B virus (HBV) biomarkers and recruited 1,209 male residents who were HBsAg positive adults aged 25-54 with normal liver function test, serum alpha-fetoprotein negative, no personal history of cancer, and no use of prescribed medications. They were consented and randomly divided into two study groups and were asked to give their blood and urine samples for the background analysis. Participants were received two capsules daily, either contained GTP 500 mg (n= 608) or placebo (n= 601) that were identical in color and size. Follow-up visits were taken every month in the participant’s house to record possible side effect complaints and to examine the actually remaining numbers of capsule to assess adherence to the dose protocol. The term of the trial was 3 years. Follow-up visit was continued for additional two years. Ninety-one percent (1,101/1,209) participants completed the trial. Among them, 90.8% (494/544) in GTP-treated group and 89.4% (489/547) in placebo control group took capsules as instructed and compiled with the dose protocol. Gastrointestinal adverse effects were noticed in some participants, 3.8 % (23/609) in GTP-treated group and 3.5% (21/601) in placebo group. No statistical significance was found between these adverse effects (p = 0.87). Ten cases of hepatocellular carcinoma (HCC) were recorded in GTP-treated group (5 in year 1, 3 in year 2, and 2 in year 3) and 18 HCC cases were recorded in placebo group (6 in year 1, 8 in year 2, and 4 in year 3). After excluding the first year HCC cases, the incidence of HCC in GTP treated group is 0.45% (5/1,112 person year) and 1.11% (12/1086 person year) with Χ² = 3.269 and p = 0.0706. These results demonstrate relative long-term safety of GTP in human intervention and administration with GTP may have protective effect against human hepatocellular carcinogenesis. (Supported by the Chinese Natural Science Foundation and CA90997 from NCI)