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Lung Cancer Chemoprevention^*

ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)

^* From the H. Lee Moffitt Cancer Center and Research Institute (Drs. Gray and Bepler), Program and Division of Thoracic Oncology, Tampa, FL; Jonsson Comprehensive Cancer Center (Dr. Mao), University of California, Los Angeles, CA; National Cancer Institute (Dr. Szabo), Bethesda, MD; Duke Comprehensive Cancer Center (Dr. Kelley), Duke University Medical Center, Durham, NC; and MD Anderson Cancer Center (Dr. Kurie), Houston, TX.

Correspondence to: Gerold Bepler, MD, PhD, Division of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, MRC-4W, Room 4046, Tampa, FL 33612; e-mail: gerold.bepler{at}moffitt.org

Background: Lung cancer is the most common cause of cancer death in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk for lung cancer compared with lifetime never-smokers. Chemoprevention is the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention.

Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations.

Results: None of the phase III trials with the agents beta carotene, retinol, 13-cis-retinoic acid, -tocopherol, N-acetylcysteine, or acetylsalicylic acid has demonstrated beneficial, reproducible results. For facilitating the evaluation of promising agents and for lessening the need for a large sample size, extensive time commitment, and expense, focus is now turning toward the assessment of surrogate end point biomarkers for lung carcinogenesis. With the understanding of important cellular signaling pathways, various inhibitors that may prevent or reverse lung carcinogenesis are being developed.

Conclusions: By integrating biological knowledge, more trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points.

Key Words: acetyl salicylic acid • apoptosis • biomarkers • chemoprevention • cyclooxygenase-2 inhibitors • lung cancer • proliferation • protein kinase C • selenium • signal transduction pathways • tyrosine kinase inhibitors • vitamin A • vitamin E

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