Progress in lung cancer chemoprevention.

BACKGROUND Lung cancer is one of the major causes of cancer-related deaths. Lung cancer mortality figures argue powerfully for new approaches to control this disease. The term chemoprevention can be defined as the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent premalignancy from progressing to invasive cancer. METHODS Issues related to lung cancer chemoprevention are reviewed, including risk factors and identification of high-risk cohorts, endpoint biomarkers, and current and new chemopreventive agents. Also, important findings from chemoprevention randomized, controlled trials are summarized. RESULTS Trials in lung cancer chemoprevention have so far produced either neutral or harmful primary endpoint results, whether in the primary, secondary, or tertiary settings. Lung cancer was not prevented by beta-carotene, alpha-tocopherol, retinol, retinyl palmitate, N-acetylcysteine, or isotretinoin in smokers. Secondary results from the phase III trials involving selenium and vitamin E, as well as results from the US Intergroup NCI I91-0001 trial supporting treatment with isotretinoin in never and former smokers, are promising and may help define new avenues for chemoprevention. CONCLUSIONS The concept of chemoprevention in lung cancer is still in its infancy but one day may have a significant impact on the incidence and mortality of this leading cancer threat. Molecular markets of risk, drug activity and targeting, improved imaging techniques, and new drug delivery systems are being evaluated.