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
Budesonide versus Placebo in a High-risk Population with Screen-detected Lung Nodules
European Oncology, 2010;6(1):15-8 DOI: http://doi.org/10.17925/EOH.2010.06.1.15
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
Correspondence: Bernardo Bonanni, Division of Cancer Prevention and Genetics, European Institute of Oncology, Via Ripamonti, 435, I-20141, Milan, Italy. E: firstname.lastname@example.org
- Jemal A, Thun MJ, Ries LA, et al., Annual report to the nation on the status of cancer, 1975–2005, featuring trends in lung cancer, tobacco use, and tobacco control, J Natl Cancer Inst, 2008;100(23):1672–94.
- Ezzati M, Henley SJ, Lopez AD, Thun MJ, Role of smoking in global and regional cancer epidemiology: current patterns and data needs, Int J Cancer, 2005;116(6):963–71.
- Yang L, Fujimoto J, Qiu D, Sakamoto N, Trends in cancer mortality in the elderly in Japan, 1970–2007, Ann Oncol, 2010;21:389–96.
- Giovino GA, The tobacco epidemic in the United States, Am J Prev Med, 2007;33(6 Suppl.):S318–S326.
- Giovino GA, Epidemiology of tobacco use in the United States, Oncogene, 2002;21(48):7326–40.
- Warner KE, Burns DM, Hardening and the hard-core smoker: concepts, evidence, and implications, Nicotine Tob Res, 2003;5(1):37–48.
- Kaneko M, Eguchi K, Ohmatsu H, et al., Peripheral lung cancer: screening and detection with low-dose spiral CT versus radiography, Radiology, 1996;201(3):798–802.
- Henschke CI, McCauley DI, Yankelevitz DF, et al., Early Lung Cancer Action Project: overall design and findings from baseline screening, Lancet, 1999;354(9173):99–105.
- Henschke CI, Naidich DP, Yankelevitz DF, et al., Early lung cancer action project: initial findings on repeat screenings, Cancer, 2001;92(1):153–9.
- Swensen SJ, Jett JR, Sloan JA, et al., Screening for lung cancer with low-dose spiral computed tomography, Am J Respir Crit Care Med, 2002;165(4):508–13.
- Diederich S, Wormanns D, Semik M, et al., Screening for early lung cancer with low-dose spiral CT: prevalence in 817 asymptomatic smokers, Radiology, 2002;222(3):773–81.
- Pastorino U, Bellomi M, Landoni C, et al., Early lungcancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results, Lancet, 2003;362(9384):593–7.
- Veronesi G, Bellomi M, Mulshine JL, et al., Lung cancer screening with low-dose computed tomography: a noninvasive diagnostic protocol for baseline lung nodules, Lung Cancer, 2008;61(3):340–49.
- Henschke CI, Yankelevitz DF, Libby DM, et al., Survival of patients with stage I lung cancer detected on CT screening, N Engl J Med, 2006;355(17):1763–71.
- Balkwill F, Mantovani A, Inflammation and cancer: back to Virchow?, Lancet, 2001;357(9255):539–45.
- Coussens LM, Werb Z, Inflammation and cancer, Nature, 2002;420(6917):860–67.
- Mantovani A, Allavena P, Sica A, Balkwill F, Cancerrelated inflammation, Nature, 2008;454(7203):436–44.
- Pereira MA, Li Y, Gunning WT, et al., Prevention of mouse lung tumors by budesonide and its modulation of biomarkers, Carcinogenesis, 2002;23(7):1185–92.
- Wang Y, Zhang Z, Kastens E, et al., Mice with alterations in both p53 and Ink4a/Arf display a striking increase in lung tumor multiplicity and progression: differential chemopreventive effect of budesonide in wild-type and mutant A/J mice, Cancer Res, 2003;63(15):4389–95.
- Alyaqoub FS, Tao L, Kramer PM, et al., Prevention of mouse lung tumors and modulation of DNA methylation by combined treatment with budesonide and R115777 (Zarnestra MT), Carcinogenesis, 2007;28(1):124–9.
- Parimon T, Chien JW, Bryson CL, et al., Inhaled corticosteroids and risk of lung cancer among patients with chronic obstructive pulmonary disease, Am J Respir Crit Care Med, 2007;175(7):712–19.
- Lam S, le Riche JC, McWilliams A, et al., A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with dysplasia of the bronchial epithelium, Clin Cancer Res, 2004;10(19):6502–11.
- van den Berg RM, Teertstra HJ, van ZN, et al., CT detected indeterminate pulmonary nodules in a chemoprevention trial of fluticasone, Lung Cancer, 2008;60(1):57–61.
- Punturieri A, Szabo E, Croxton TL, et al., Lung cancer and chronic obstructive pulmonary disease: needs and opportunities for integrated research, J Natl Cancer Inst, 2009;101(8):554–9.
- The Alpha-Tocopherol BCCPSG. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers, N Engl J Med, 1994;330(15): 1029–35.
- Lee JS, Lippman SM, Benner SE, et al., Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia, J Clin Oncol, 1994;12(5): 937–45.
- Kim HY, Shim YM, Lee KS, et al., Persistent pulmonary nodular ground-glass opacity at thin-section CT: histopathologic comparisons, Radiology, 2007;245(1): 267–75.
- Lee HJ, Goo JM, Lee CH, et al., Predictive CT findings of malignancy in ground-glass nodules on thin-section chest CT: the effects on radiologist performance, Eur Radiol, 2009; 19(3):552–60.
- Pelosi G, Sonzogni A, Veronesi G, et al., Pathologic and molecular features of screening low-dose computed tomography (LDCT)-detected lung cancer: a baseline and 2-year repeat study, Lung Cancer, 2008;62(2):202–14.
Keywords: Budesonide, chemoprevention, lung cancer