Budesonide versus Placebo in a High-risk Population with Screen-detected Lung Nodules

European Oncology, 2010;6(1):15-8

Abstract:

Screening computed tomography (CT) enables the detection of small peripheral lung nodules. The nature of these nodules is uncertain, but it seems reasonable that some of them, in particular non-solid nodules, could represent pre-cancerous lesions. A previous trial showed a reduction in the size of peripheral nodules by inhaled budesonide in subjects with bronchial dysplasia. We tested inhaled budesonide 800μg or placebo twice daily in a randomised, double-blind, placebo-controlled phase IIb trial, which enrolled 202 current and former smokers with stable CT-detected lung nodules. The primary end-point was the one-year change in target nodule size in a per-subject analysis. Treatment was well tolerated and >80% of participants received at least 50% of total drug dose. Initial observations seem to show a promising effect on non-solid target nodules in individuals at high risk of lung cancer. As non-solid nodules may represent precursors of adenocarcinoma, further investigations in this population are warranted.

Acknowledgements: This work was supported by National Cancer Institute grant number N01-CN-35159). Drug and placebo were provided by AstraZeneca, Sweden.
Keywords: Budesonide, chemoprevention, lung cancer
Disclosure: The authors have no conflicts of interest to declare.
Received: September 23, 2009 Accepted March 16, 2010 Citation European Oncology, 2010;6(1):15-8
Correspondence: Bernardo Bonanni, Division of Cancer Prevention and Genetics, European Institute of Oncology, Via Ripamonti, 435, I-20141, Milan, Italy. E: bernardo.bonanni@ieo.it

Lung cancer is the most common cause of cancer-related death in both men and women,1 and smoking is the largest avoidable cause of death worldwide.2 Smoking has consistently been recognised as the main aetiological factor for lung cancer, accounting for ~85–90% of cases, and the increased risk of developing lung cancer persists many years after stopping smoking.3 Thanks to smoking cessation programmes, the rate of decrease in the prevalence of adult smoking in the US increased significantly in recent years, but from 2004 to 2007 this rate remained at about 20%.4 This plateau of decline in smoking has been explained by a possible levelling-out in smoking cessation success,5 suggesting that the remaining population of smokers can be considered unable or unwilling to quit.6 Both current and former smokers are the target population who may benefit from a chemopreventative strategy because of its potential to arrest or revert the cancerogenesis progression. Unfortunately, researchers have yet to succeed in developing an effective chemopreventative strategy against lung cancerogenesis. Moreover, the majority of trials conducted so far were focused on the potential effect on bronchial dysplasia and not on the peripheral lung, where most lung cancers actually arise.7

Computed Tomography and Screening

The screening computed tomography (CT) is a non-invasive test with low radiation exposure and no contrast medium. It provides the opportunity to study the peripheral lung area despite the limitations of characterising the nature of small lesions that cannot undergo biopsy. So far, many observational studies have demonstrated that low-dose CT is a sensitive tool for the identification of early lung cancer,8–13 and a 10-year survival rate of 88% was estimated for stage I screen-detected cases.14

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Keywords: Budesonide, chemoprevention, lung cancer
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