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CLINICAL TRIALS OF GREEN TEA
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- 7.1. Chemoprevention trials
- 7.1.1. Breast cancer
- 7.1.2. Prostate cancer
- 7.1.3. Lung cancer
- 7.1.4. Chronic lymphocytic leukemia (CLL)
- 7.2. Combinational treatments
- 7.3. Issues related to cancer therapy with green tea
7. CLINICAL TRIALS OF GREEN TEAThe effects of tea polyphenols are widely studied for cancer chemoprevention in many different parts of the world. Several excellent reviews compiling results of such studies are available (135). Unfortunately, the lack of a firm conclusion still exists in spite of bundle of reviews and papers that have been written on green tea. One apparent reason is etiological factors for different types of cancers are not the same and the populations studied are different. From the available data of epidemiologic studies and research findings in laboratory, clinical trials are now warranted to evaluate the usefulness of green tea and polyphenols present therein. The first such trial was conducted by the MD Anderson Cancer Center in collaboration with the Memorial Sloan-Kettering Cancer Center. Research suggests that green tea consumption has promising effects against various types of cancers without inducing major toxicities. Studies using green tea in the treatment of cancers have focused on breast, prostate and lung cancers as well as recently on chronic lymphocytic leukemia (CLL) (136). 7.1. Chemoprevention trialsCancer chemoprevention, as first defined by Sporn in 1976, uses natural, synthetic, or biological chemical agents to reverse, suppress, or prevent carcinogenic progression (137). Chemoprevention trials are based on the hypothesis that interruption of the biological processes involved in carcinogenesis will inhibit this process and, in turn, reduce cancer incidence (138). 7.1.1. Breast cancerA randomized phase I clinical trial was conducted by M.D. Anderson Cancer Center studying the side effects and best dose of green tea extract in treating women with hormone receptor-negative stage I, stage II, or stage III breast cancer (NCT00516243). Patients were randomized to 1 of 2 treatment arms. Arm I: Patients received 1 of 3 dosages of oral green tea extract (Polyphenon E) twice daily for 6 months in the absence of disease progression or unacceptable toxicity. Arm II: Patients received oral placebo twice daily for 6 months in the absence of disease progression or unacceptable toxicity. More clinical trials are needed to evaluate its biological activities and molecular targets in patients. Another phase II trial (NCT00917735) conducted by clinical and Translational Science Institute of University of Minnesota studying the efficacy of green tea extracts in reducing the risk of breast cancer. In this ongoing clinical trial, patients are given two capsules of green tea extracts twice daily. The investigators are evaluating the efficacy of green tea extracts by analyzing the different breast cancer markers such as plasma insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), estrone, estradiol, androstenedione, sex hormone binding globulin (SHBG), urinary estrogen metabolites and plasma F2-isoprostanes. 7.1.2. Prostate cancerIn a very interesting study, the effects of green tea on premalignant lesions with a daily treatment of 600 mg green tea capsules in 60 patients with high grade prostate cancer shows 30% incidence among the 30 placebo treated subjects and only 3% incidence among green tea treated subjects. No significant side effects or adverse effects were documented (139). Another phase II clinical trial conducted by multiple institutions, evaluated the effect of green tea on patients without symptoms of prostate cancer but with biopsy proven malignancy and clinical evidence of androgen independent disease. Patients were given the dose of 6 g/day for 6 months and each dose of green tea powder contains 100 calorie and 46 mg of caffeine. Among 42 patients one patient had shown tumor response defined by 50% decrease in PSA from baseline (229 ng/dl to 105 ng/dl), however this effect was not sustained beyond 2 months (140). The overall response rate was only 2% and after one month the median change in PSA from baseline was found to be increased. Even the radiographic and physical examination shows no biochemical tumor response (141). A single institutional prospective clinical trial, evaluated the effect of standardized green tea extract (GTE) on 19 patients having progressive hormone-refractory prostate cancer. The median age of the patients in this study was 76 years old and was administrated 250 mg of green tea extract twice daily. Each capsule contains 30% of EGCG and less than 2% caffeine. Out of 19 patients, 15 took GTE for 2 months and remaining was found to have progressive disease. Only one patient demonstrated a modest decrease of PSA but that lasted for only two months. An issue related with study was lower dose of GTE. According to pharmacokinetics studies of Polyphenon E 400 to 1200 mg of EGCG should be given and thus it is 2 to 8 fold less than the actual dose 500mg/day. In summary this study provides some valuable insights that patients with late stage of hormone refractory prostate cancer are not the ideal population for the treatment of green tea.
Data available from various clinical trials on different types of cancer suggests that green tea polyphenol EGCG provides a rationale for exploring this compound in chemoprevention and as hematologic malignancies in prostate cancer. 7.1.4. Chronic lymphocytic leukemia (CLL)In vitro studies have shown that EGCG can induce apoptotic cell death in leukemic B-cells from a majority of patients with chronic lymphocytic leukemia (CLL). Mayo clinic reported an interesting observation in patients with CLL and low grade lymphoma who self administered over-the-counter green tea products. Patients with steady clinical, laboratory, and/or radiographic evidence of progression prior to initiation of over-the-counter green tea products had developed an objective response after this therapy (143). Another study was conducted to investigate the optimal dose and tolerability of patients with chronic lymphocytic leukemia (CLL) to Polyphenone E. Three to six patients were given 400 to 2000 mg capsules (twice a day) of Polyphenon E with a standardized dose of epigallocatechin-3-gallate (EGCG) with asymptomatic Rai stage 0 to II CLL. Majority of patients showed decreased levels in absolute lymphocyte count (ALC) and /or lymphoadenopathy in phase I trial. This treatment was very well tolerated and suggests that Polyphenon E merits additional evaluation as a disease-stabilizing agent (136). 7.2. Combinational treatmentsStudies using a human carcinoma xenograft model established with resistant human oral epidermoid carcinoma cells indicated that the combination of doxorubicin with EGCG increased the doxorubicin concentration in the tumors by 51% and increased apoptosis in the tumors compared with doxorubicin alone (144). Moreover, the combination of EGCG and tamoxifen has been shown to synergistically induce apoptosis and growth inhibition in MDA-MB-231 human breast cancer cells (145). A randomized phase II trial is studying how well giving erlotinib together with GTE works in preventing cancer recurrence in former smokers who have undergone surgery for bladder cancer. As a chemosensitizer, EGCG has been shown to increase cisplatin potency by three to six fold in ovarian cancer cells (SKOV3, CAOV3, and C200 cells), including one cell line that exhibits several hundredfold resistance to cisplatin over the other cells. The addition of EGCG amplified the toxicity of cisplatin. The finding suggests that ovarian cancer cells are susceptible to the pro-oxidant activity of EGCG is very important (146). Its capacity to differentially influence the cancerous versus and normal cells may ease the problem of cisplatin toxicity and resistance, a key obstacle in chemotherapy for ovarian cancer. 7.3. Issues related to cancer therapy with green teaModerate intake of green tea is generally considered safe. Asians have consumed tea for thousands of years with few dangerous side effects. Drinking large amounts of tea may cause nutritional and other problems because of the caffeine content and the strong binding activities of the polyphenols, which can make it harder for the body to absorb certain medicines and iron supplements. Possible effects from too much caffeine are the major concern with green tea. In mice, it has been found that long-term consumption of low dose caffeine slowed the hippocampus-dependent learning and impaired long-term memory (147). Another possible reason for potential adverse effects of green tea is the drug and green tea interactions. The combination of green tea and chemotherapy medications, specifically bortezomib (BZM; Velcade) interacts with each other thus preventing apoptosis. Recent studies show that various green tea components, in particularly EGCG and other polyphenols with 1, 2-benzenediol moieties, effectively prevented tumor cell death induced by BZM. Taken together, results indicates that green tea polyphenols may have the potential to reverse the therapeutic efficacy of BZM, namely via direct chemical inactivation of BZM. And thereby preventing its biological activity, that one would expect that not only the therapeutic efficacy but it also emergence some side effects that usually accompany BZM therapy (148). Authors strongly suggest that while investigating on the combinational therapies with natural compounds, potential nutrition-drug interactions should also be kept in mind. However, these results have not yet been demonstrated sufficiently in studies on humans. On the other hand, there have been reports of both green and black tea extracts stimulating a gene in prostate cancer cells that may cause them to be less sensitive to chemotherapy drugs. Given this potential interaction, people might not drink black and green tea (as well as extracts of these teas) while receiving chemotherapy for prostate cancer in particular. The adverse effect of green tea consumption has also been studied. One such evidence suggests that green tea has adverse effects on central nervous system (CNS) and gastrointestinal system (GI). The present study investigates the green tea extract on human s with HTLV-1 reported patients. Thirty-seven subjects were followed up for 5 months by measuring HTLV-1 provirus load after daily intake of 9 capsules of green tea extract powder per day. 12 patients were reported difficulties with monthly donation of blood samples and low compliance with the daily intake of GTE. Two clinical trials investigated the efficacy of green tea on different stages of prostate cancer. The aggressive and advanced stage of prostate cancer shows mild, moderate and severe toxicities in GI and CNS (149). According to Jatoi et al (140), 69% of patients reported toxicity but only one patient had experienced the severe confusion and grade IV toxicity. Go to: жүктеу/скачать 1.88 Mb. Достарыңызбен бөлісу:
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