Chemoprevention of Nonmelanoma Skin Cancer: Experience with a Polyphenol from Green Tea
Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precan cerous changes. Epidemiologic evide
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Abstract Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed.
Background Nonmelanoma skin cancer is a significant and increasing medical problem. In the United States, over one million new cases of nonmelanoma skin cancer are diagnosed each year, probably exceeding the incidence of all other types of cancer combined (Jemal et al. 2002). The two most common types of nonmelanoma skin cancer are basal cell carcinoma and squamous cell carcinoma. The greatest risk factors for these types of cancers are a fair skin type and high cumulative exposure to sunlight. The most readily identifiable premalignant lesion for nonmelanoma skin cancers is actinic keratosis (solar keratosis), which is considered to be a premalignant precursor to squamous cell carcinoma. There is some controversy over this designation among dermatologists, some of whom consider actinic keratoses to be a form of squamous cell carcinoma in situ of the skin (Heaphy and Ackerman 2000). The risk factors for actinic keratoses are the same as Recent Results in Cancer Research, Vol. 163 © Springer-Verlag Berlin Heidelberg 2003
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those for nonmelanoma skin cancer, as described above. Given these risk factors, it is not surprising that fair-skinned populations inhabiting sunny climates at latitudes closer to the equator such as Australia have the highest risk for, and incidence of, actinic keratoses (Marks 1990). Actinic keratoses are readily identifiable precursors to nonmelanoma skin cancer; as a result they are useful clinical markers for cancer prevention research. Interventions that lead to the regression or decrease in the rate of formation of actinic keratoses would be expected to lead to a decrease in the formation of nonmelanoma skin cancers, particularly squamous cell carcinoma of the skin. It is for this reason that actinic keratoses are being extensively studied as modulable clinical endpoints in trials testing the chemopreventive potential of promising agents against the development of nonmelanoma skin cancer. The purpose of this chapter is to discuss important aspects of study design for clinical trials of potential chemopreventive agents administered to prevent, regress, or retard the development of actinic keratoses and nonmelanoma skin cancer. Our experiences with a polyphenol from green t
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