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Chemoprevention of Cancers of the Upper Aerodigestive Tract Smoking causes diffuse epithelial injury in the head, neck, esophagus, and lung. Patients cured of squamous cell cancers of the lung, esophagus, head, and neck are at risk (as high as 5% per year) of developing second cancers of the upper aerodigestive tract. Cessation of cigarette smoking does not markedly decrease the cured cancer patient's risk of second malignancy, even though it does lower the cancer risk in those who have never developed a malignancy. Smoking cessation may halt the early stages of the carcinogenic process (such as metaplasia), but it. | Chapter 078. Prevention and Early Detection of Cancer Part 4 Chemoprevention of Cancers of the Upper Aerodigestive Tract Smoking causes diffuse epithelial injury in the head neck esophagus and lung. Patients cured of squamous cell cancers of the lung esophagus head and neck are at risk as high as 5 per year of developing second cancers of the upper aerodigestive tract. Cessation of cigarette smoking does not markedly decrease the cured cancer patient s risk of second malignancy even though it does lower the cancer risk in those who have never developed a malignancy. Smoking cessation may halt the early stages of the carcinogenic process such as metaplasia but it may have no effect on late stages of carcinogenesis. This field carcinogenesis hypothesis for upper aerodigestive tract cancer has made cured patients an important population for chemoprevention of second malignancies. Oral leukoplakia a premalignant lesion commonly found in smokers has been used as an intermediate marker allowing demonstration of chemopreventive activity in smaller shorter duration randomized placebo-controlled trials. Response was associated with upregulation of retinoic acid receptor-0 RAR-0 . Therapy with high relatively toxic doses of isoretinoin 13-cis-retinoic acid causes regression of oral leukoplakia. However the lesions recur when the therapy is withdrawn suggesting the need for chronic administration. More tolerable doses of isoretinoin have not proven beneficial in the prevention of head and neck cancer. Isoretinoin also failed to prevent second malignancies in patients cured of early-stage non-small cell lung cancer mortality rates were actually increased in current smokers. Premalignant lesions in the oropharyngeal area have also responded to retinol a-tocopherol vitamin E and selenium. Further study to define the activity of these drugs is ongoing. Several large-scale trials have assessed agents in the chemoprevention of lung cancer in patients at high risk. In the .
