Chemoprevention of Lung Cancer: New Directions
The refractoriness of advanced lung cancer to current treatment modalities requires new approaches to reduce the public health burden associated with this disease. One strategy that is currently being tested is chemoprevention, which aims to prevent the d
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Abstract The refractoriness of advanced lung cancer to current treatment modalities requires new approaches to reduce the public health burden associated with this disease. One strategy that is currently being tested is chemoprevention, which aims to prevent the development of cancer in populations that are at high risk for cancer due to a variety of genetic or environmental factors. The key to the success of this approach, however, requires the identification of appropriately targeted efficacious, non-toxic agents as well as the methodologies to efficiently test them. Given the lack of success of previous phase III definitive lung cancer chemoprevention trials, there is a need for smaller scale phase II trials with molecular, imaging, or histologic endpoints to demonstrate preliminary safety and efficacy. The identification of molecular pathways critical to lung carcinogenesis offers the opportunity to develop targeted therapies for prevention. Means of optimizing the risk/benefit ratio associated with treatment include regional drug delivery that minimizes systemic toxicities and combination therapies. Identification of the most appropriate cohorts, such as former smokers without ongoing DNA damage due to carcinogen exposure, may uncover benefits that are hidden in a mixed population. Equally important is the identification of appropriate study endpoints that are predictive of patient outcomes such as cancer incidence. Further understanding of lung cancer biology will be critical to the success of future clinical trials.
Introduction Despite major advances in our understanding of the molecular pathogenesis of lung cancer, survival after the diagnosis of lung cancer has not improved significantly over the past several decades (Greenlee et al. 2001). Lung cancer continues to be a leading cause of death worldwide, with an estimated l.2 milRecent Results in Cancer Research, Vol. 163 © Springer-Verlag Berlin Heidelberg 2003
Chemoprevention of Lung Cancer: New Directions
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lion new cases in 2000 (Parkin 2001). In the United States alone, there were an estimated 169,500 new cases and 157,400 deaths in 2001 (Greenlee et al. 2001). The 5-year survival rate of 14% has not improved appreciably since the 1970s, primarily due to the relatively late stage at diagnosis. The refractory nature of advanced disease to current treatment modalities mandates the development of alternate strategies to reduce its public health burden. Targeting early phases of carcinogenesis that may be more amenable to treatment, thereby preventing the development of invasive and metastatic disease, offers one such attractive option. However, progress in prevention science depends on simultaneous advances in the identification of targeted, nontoxic agents and in the development of methodologies to evaluate promising new agents efficiently and appropriately. Definitive phase III cancer prevention trials with cancer incidence endpoints require thousands of patients, substantial resources, and many years for completion. Therefore, phase II studies
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