The study was the work of senior author Dr Vassiliki Papadimitrakopoulou, professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, and colleagues, and was published online on 1 November in the journal Cancer Prevention Research.
Figures from the American Cancer Society show that more than 35,720 Americans are expected to be diagnosed with oral and/or pharynx cancer in 2009 and the five year survival rate is less than 50 per cent.
Previous clinical studies have showed mixed results with trying to measure the effectiveness of green tea as a cancer prevention agent, although as the authors wrote in their background information:
“Epidemiologic and preclinical data support the oral cancer prevention potential of green tea extract.”
So they set up a Phase II dose-finding trial, purported to be the first study of its kind, to examine green tea as a chemopreventative agent in this high-risk patient population.
The results showed that more than half of the patients with oral leukoplakia who took the green tea extract had a clinical response.
Papadimitrakopoulou told the press that:
“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.”
“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,” she explained.
For the study, between August 2002 and March 2008, Papadimitrakopoulou and colleagues randomized 41 oral leukoplakia patients from the MD Anderson Cancer Center to receive either green tea extract or placebo.
In the extract group, patients received the extract orally for three months at one of three doses: 500 per meter squared of body mass (mg/m2); 750 mg/m2 or 1,000 mg/m2, taken three times a day.
Just before they started taking the doses all patients underwent a biopsy, and then had another 12 weeks later. The authors said this was the best way to assess biomarkers and formed an important and crucial part of the study design.
First author Dr Anne Tsao, assistant professor in the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson said:
“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 anti-angiogenic effects as a potential mechanism of action.”
“While preliminary because our patient population was so small, this gives us direction for further study,” she added.
The results showed that:
- Of the patients taking the highest two doses of green tea extract, 58.8 per cent had a clinical response.
- This compared with 36.4 per cent of those taking the lowest dose, and 18.2 per cent of those taking placebo.
- After a mean extended follow up period of 27.5 months, 15 of the participants had developed oral cancer, with a median time to disease development of 46.4 months.
- The patients treated with green tea extract also showed improved histology , although this was shown not to be statistically significant (21.4 per cent versus 9.1 per cent in the placebo group; P = 0.65).
- Green tea extract was well tolerated, although those on the highest doses had increased insomnia/nervousness, it produced no grade 4 toxicity, wrote the authors.
The authors also reported that green tea extract showed a trend toward improvement in a number, but not all, of the biomarkers that play an important role in predicting cancer development.
They concluded that green tea extract may suppress oral pre-malignant lesions, in part through reducing angiogenic stimulus through its effect on stromal vascular endothelial growth factor (stromal VEGF).
Higher doses of green tea extract may also improve short-term (12-week) outcomes on oral pre-malignant lesions, they wrote, and suggested that:
“The present results support longer-term clinical testing of GTE [green tea extract] for oral cancer prevention.”
“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,” she added, explaining that they still need to “further understand if green tea offers longer-term prevention effects for patients.”
Papadimitrakopoulo and Tsao suggest that further research on the effects of green tea extract in this high-risk population should concentrate on participants taking it for a longer period.
The researchers also wished to point out that the green tea extract they used in the study was not available over the counter or on the Internet, neither commercial sources being highly regulated. They used a compound that had been developed exclusively as a pharmaceutical agent.
“Phase II Randomized, Placebo-Controlled Trial of Green Tea Extract in Patients with High-Risk Oral Premalignant Lesions.”
Anne S. Tsao, Diane Liu, Jack Martin, Xi-ming Tang, J. Jack Lee, Adel K. El-Naggar, Ignacio Wistuba, Kirk S. Culotta, Li Mao, Ann Gillenwater, Yuko M. Sagesaka, Waun K. Hong, and Vassiliki Papadimitrakopoulou.
Cancer Prevention Research, 2: 931-941, November 1, 2009
Additional sources: University of Texas MD Anderson Cancer Center, American Cancer Society.
Written by: Catharine Paddock, PhD