Green Tea Shows Chemopreventive Potential for Oral Cancer

Green tea extract has shown promise as cancer prevention agent for oral cancer in patients with a premalignant condition known as oral leukoplakia.

The study, conducted by investigators from the University of Texas M.D. Anderson Cancer Center (Houston, USA), and published online in November 2009 in the journal Cancer Prevention Research, is the first to evaluate green tea as a chemopreventive agent in this high-risk patient population. The researchers discovered that more than half of the oral leukoplakia patients who took the extract had a clinical response.

Extensively studied in laboratory, epidemiological, and clinical settings for several cancer types, green tea is rich in polyphenols, which have been known to suppress carcinogenesis in preclinical models. Still, clinical results have been mixed. "While still very early, and not definitive proof that green tea is an effective preventive agent, these results certainly encourage more study for patients at highest risk for oral cancer,” said Vassiliki Papadimitrakopoulou, M.D., professor in M.D. Anderson's department of thoracic/head and neck medical oncology, and the study's senior author. "The extract's lack of toxicity is attractive--in prevention trials, it's very important to remember that these are otherwise healthy individuals and we need to ensure that agents studied produce no harm.”

In the phase II dose-finding study, 41 M.D. Anderson oral leukoplakia patients were randomized between August 2002 and March 2008 to receive either green tea extract or placebo. Participants took the extract, an oral agent, for three months at one of three doses--500 mg per meter squared of body mass (mg/m2); 750 mg/m2 or 1,000 mg/m2--three times daily. To best assess biomarkers, participants also underwent a baseline and 12-week biopsy, an important component in the design of the study, according to the investigators.

"Collecting oral tissue biopsies was essential in that it allowed us to learn that not only did the green tea extract appear to have benefit for some patients, but we pointed to antiangiogenic effects as a potential mechanism of action,” said Anne Tsao, M.D., assistant professor in the department of thoracic/head and neck medical oncology, and the study's first author. "While preliminary because our patient population was so small, this gives us direction for further study.”

Of those taking green tea at the two highest doses, 58.8% had a clinical response, compared with 36.4% in the lowest extract dose and 18.2% in the placebo arm. At an extended follow-up with a mean of 27.5 months, 15 participants had developed oral cancer, with a median time to disease development of 46.4 months.

Although not statistically significant, the green tea extract also improved histology and trended towards an improvement in a number of biomarkers that may play a critical role in predicting cancer development.

Another important finding, according to the researchers, was that that the extract was well tolerated. Side effects, including insomnia and nervousness, were mostly seen in the high-dose group but these produced no significant toxicity. "While these are encouraging findings, much more research must be done before we can conclude that green tea may prevent oral or any other type of cancer. It's also important to remind people that this trial enrolled very few participants who, at the highest dose levels took the equivalent of eight cups of green tea three times a day,” said Dr. Papadimitrakopoulou. "We need to further understand if green tea offers longer-term prevention effects for patients.”

Drs. Papadimitrakopoulou and Tsao believe that future studies with green tea in this high-risk population should focus on participants being exposed to the supplement for a longer period. The researchers also stressed that the green tea extract assessed in this trial was never sold over-the-counter and/or the Internet, both of which are not highly regulated. Instead, the compound was exclusively developed as a pharmaceutical.

The study was funded by Ito En, Ltd. (Tokyo, Japan), the company that produced the green tea extract.

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University of Texas M.D. Anderson Cancer Center