CHEMOPREVENTION OF RESPIRATORY-TRACT CANCER

Lung cancer is the leading cause of cancer death in the United States, and advances in therapy have accounted for an improvement in five-yea r survival in this disease from 9% to 13% over the last three decades. Molecular genetic evidence has confirmed the epidemiologic link betwe en tobacco and lung cancer causation, and has clarified the etiology o f the persistent risk of lung cancer development in former smokers. Re tinoids have shown promise in aerodigestive cancer chemoprevention, bo th in the reversal of preneoplastic lesions and in the prevention of s econd primary cancers. After initial epidemiologic and dietary studies had Linked P-Carotene with cancer risk reduction, large randomized ph ase III studies of this compound have shown no evidence of benefit and some evidence of heightened lung cancer risk in active smokers on hig h dose supplemental B-Carotene. Therefore, careful clinical, epidemiol ogic, and basic studies of retinoids using intermediate end point mark ers are necessary to determine the definitive role of these compounds in the chemoprevention of respiratory tract cancer, with a particular focus on former smokers.