For centuries, consumption of green tea was known anecdotally to alleviate symptoms from a wide variety of ailments. In the 1906 classic The Book of Tea, Japanese scholar Okakura Kakuzo tells us that tea "was highly prized for possessing the virtues of relieving fatigue, delighting the soul, strengthening the will, and repairing the eyesight." In the 1940s and 1950s, research on the chemical composition of the tea plant (Camellia sinensis) revealed a powerful antioxidant, epigallocatechin gallate (EGCG), as the major polyphenolic constituent and the substance most likely responsible for conferring health benefits. This early work led to an explosion in research on green tea polyphenols, with a recent human clinical trial suggesting their potential in the treatment of chronic lymphocytic leukemia. It seems the drink that "began as a medicine and grew into a beverage" may have finally come full circle.
Shanafelt, T. D.; Call, T. G.; Zent, C. S.; La Plant, B.; Bowen, D. A.; Roos, M.; Secreto, C. R.; Ghosh, A. K.; Kabat, B. F.; Lee, M.-J.; Yang, C.; Jelinek, D. F.; Erlichman, C.; Kay, N. E. Phase I trial of daily oral polyphenon E in patients with asymptomatic Rai state 0 to II chronic lymphocytic leukemia. J. Clin. Oncol. 2009, 27 (23), 3808-3814. To define the optimal dose of Polyphenon E for chronic daily administration and tolerability in patients with chronic lymphocytic leukemia (CLL). Previously untreated patients with asymptomatic Rai stage 0 to II CLL were eligible for participation. Polyphenon E with a standardized dose of epigallocatechin-3-gallate (EGCG) was administered using the std. phase I design with three to six patients per dose level (range, 400 to 2000 mg by mouth twice a day). Trough plasma EGCG levels were measured 1 mo after initiation of therapy. Response was classified using the National Cancer Institute (NCI) Working Group (WG) Criteria. Thirty-three eligible patients were accrued to dose levels 1 to 8. The max.-tolerated dose was not reached. The most common adverse effects included transaminitis (33%, all grade 1), abdominal pain (30% grade 1, 0% grade 2, and 3% grade 3), and nausea (39% grade 1 and 9% grade 2). One patient experienced an NCI WG partial remission. Other signs of clin. activity were also obsd., with 11 patients (33%) having a sustained ≥ 20% redn. in abs. lymphocyte count (ALC) and 11 (92%) of 12 patients with palpable adenopathy experiencing at least a 50% redn. in the sum of the products of all nodal areas during treatment. Trough plasma EGCG levels after 1 mo of treatment ranged from 2.9 to 3974 ng/mL (median, 40.4 ng/mL). Daily oral EGCG in the Polyphenon E prepn. was well tolerated by CLL patients in this phase I trial. Declines in ALC and/or lymphadenopathy were obsd. in the majority of patients. A phase II trial to evaluate efficacy using 2000 mg twice a day began in Nov. 2007.
