Key issues in lung cancer chemoprevention trials of new agents.
Lung cancer is a major health problem world-wide. Former heavy smokers retain a significant risk for lung cancer after smoking cessation. With a large population of current and former smokers at risk, an alternative cancer control strategy such as chemoprevention needs to be developed to reduce lung cancer mortality especially for smokers who have followed medical advice to give up smoking. Currently, there is no agent that has been shown to be effective in preventing lung cancer. Key issues that need to be addressed in phase II trials of promising chemopreventive agents include selection of high-risk subjects, potential variation in response due to differences in gender and smoking history as well as the choice of surrogate endpoint biomarkers. Sputum biomarkers such as image analysis of sputum cells and detection of aberrant methylation hold promise in identifying those at highest risk for chemopreventive intervention. Autofluorescence bronchoscopy is an effective method to localize dysplastic lesions to evaluate the efficacy of new chemopreventive agents. Novel imaging methods such as confocal micro-endoscopy and spiral CT-directed endoscopic biopsies are under development to evaluate the response of chemopreventive agents on peripheral pre-neoplastic lesions in small airways.
Lam
Stephen
S
Lung Tumour Group, The British Columbia Cancer Agency and The University of British Columbia, West 10 Avenue, Vancouver, BC V5Z 4E6, Canada.
MacAulay
Calum
C
LeRiche
Jean C
JC
Gazdar
Adi F
AF
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D018890:Chemoprevention / Q000379:methods; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000517:prevention & control*; D012307:Risk Factors
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor