Progress in Lung Cancer Chemoprevention

Victor Cohen, MD, Fadlo R. Khuri, MD

Disclosures

Cancer Control. 2003;10(4) 

In This Article

Abstract and Introduction

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.

Lung cancer is the most common cause of cancer mortality worldwide, with over 1.3 million deaths and continues to be a major health problem. In the United States, the disease has been the leading cause of cancer in men for years, and since 1988 it has also become the number one cause of cancer death in women. It is estimated that in the year 2002, approximately 169,400 people will be diagnosed with lung cancer and 154,900 will die of the disease, surpassing the combined death rates of breast, prostate, and colon cancers.[1]

Aggressive local control by surgical resection and/or radiation ablation is currently the mainstay of lung cancer therapy for early-stage disease. Systemic chemotherapy has been used in an attempt to prolong symptom-free survival in patients deemed unresectable or in those with metastatic disease. These interventions have produced slight declines in mortality rates in recent years; however, it appears unlikely that additional marked improvements with these practices alone will occur in the near future.[2,3,4] This grim overview argues powerfully for new, emerging approaches such as biologic or molecularly targeted therapy and chemoprevention for controlling lung cancer. Chemoprevention first described by Sporn[5] in 1976 can be defined as "the use of specific natural or synthetic chemical agents to reverse, suppress or prevent carcinogenic progression to invasive cancer." This review focuses on several issues related to lung cancer chemoprevention, including risk factors and identification of high-risk cohorts, endpoint biomarkers, and current and new chemopreventive agents. Also, the results of clinical chemoprevention trials are reviewed.

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