Scott M. Lippman, MD, FACP

Head and neck cancers are a diverse group of diseases, each with its own distinct epidemiologic, anatomic, and pathologic features, natural history, and treatment considerations. Despite improvements in diagnosis and local management, long-term survival rates for patients with this disease have not increased significantly over the past 30 years and are among the lowest for the major cancers.

This two-part series provides an up-to-date summary of the various chemopreventive agents currently in development and testing. Part 1, published in last month’s issue, focused on the retinoids, such as all-trans-

Cancer chemoprevention is the use of specific natural or synthetic substances with the objective of reversing, suppressing, or preventing carcinogenic progression to invasive cancer. Currently, numerous chemopreventive agents are in various stages of development and testing. Part 1 of this two-part series provides an overview of issues unique to chemoprevention trials, including the use of surrogate biomarkers as end points. This is followed by a discussion of the retinoids, such as all-trans-retinoic acid (ATRA [Vesanoid]), 9-cis-retinoic acid (9cRA), and isotretinoin (Accutane), and the carotenoids (eg, beta-carotene and lycopene) and other "classic" antioxidants (eg, vitamins E and C and selenium). Research on these agents will be delineated by disease site when applicable. Part 2, which will appear in next month’s issue, will focus on hormonally mediated chemopreventive agents, such as tamoxifen (Nolvadex), finasteride (Proscar), oral contraceptives, and dehydroepiandrosterone (DHEA). Part 2 also will cover nonantioxidant natural agents, such as calcium, the polyphenols, the isothiocyanates, and genistein; nonsteroidal anti-inflammatory drugs (NSAIDS), such as celecoxib, sulindac sulfone, and aspirin; difluro-methylornithine (DFMO [Eflornithine]); oltipraz; and N-acetylcysteine. [ONCOLOGY(11):1643-1658, 1998]

Clinical trials have suggested that retinoid chemoprevention prevents the development of second primary tumors following head and neck or non-small-cell lung cancer. The findings of these initial studies are now being