A Randomized Phase IIb Trial of Pulmicort Turbuhaler (Budesonide) in People with Dysplasia of the Bronchial Epithelium

• Published in: Clinical cancer research 2004-10, Vol.10 (19), p.6502-6511
• Main Authors: LAM, Stephen, LERICHE, Jean C, GAZDAR, Adi, MCWILLIAMS, Annette, MACAULAY, Calum, DYACHKOVA, Yulia, SZABO, Eva, MAYO, John, SCHELLENBERG, Robert, COLDMAN, Andy, HAWK, Ernest
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adult; Aged; Antineoplastic agents; Biological and medical sciences; Biopsy; Bronchi - chemistry; Bronchi - drug effects; Bronchi - pathology; Bronchodilator Agents - adverse effects; Bronchodilator Agents - therapeutic use; Budesonide - adverse effects; Budesonide - therapeutic use; Cough - chemically induced; Double-Blind Method; Fatigue - chemically induced; Female; Headache - chemically induced; Humans; Immunohistochemistry; Ki-67 Antigen - analysis; Logistic Models; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pharynx - drug effects; Pharynx - pathology; Precancerous Conditions - drug therapy; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Proto-Oncogene Proteins c-bcl-2 - analysis; Respiratory Mucosa - chemistry; Respiratory Mucosa - drug effects; Respiratory Mucosa - pathology; Treatment Outcome; Tumor Suppressor Protein p53 - analysis; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0686

Purpose: Preclinical studies suggest that inhaled budesonide may be an effective chemopreventive agent for lung cancer. We conducted a phase IIb study to determine the effects of inhaled budesonide in smokers with bronchial dysplasia. Experimental Design: A total of 112 smokers with more than or equal to one site of bronchial dysplasia > 1.2 mm in size identified by autofluorescence bronchoscopy-directed biopsy was randomly assigned to receive placebo or budesonide (Pulmicort Turbuhaler) 800 μg twice daily inhalation for 6 months. The primary end point was change in the histopathologic grade on repeat biopsy of the same sites at the end of 6 months. Results: There were no significant differences in the regression or progression rates of bronchial dysplasia between the two groups. There was a statistically significant but modest decrease in p53 and Bcl II expression in the bronchial biopsies after 6 months of Pulmicort Turbuhaler versus placebo ( P = 0.01 and P = 0.001, respectively). There was a small but statistically significant decrease in the proportion of computed tomography-detected lung nodules after Pulmicort Turbuhaler compared with placebo ( P = 0.024). Conclusions: Our results suggest that in smokers, inhaled budesonide in the dose of 1600 μg daily for 6 months had no effect in regression of bronchial dysplastic lesions or prevention of new lesions. Budesonide treatment resulted in a modest decrease in p53 and Bcl II protein expression in bronchial biopsies and a slightly higher rate of resolution of computed tomography-detected lung nodules. Whether budesonide truly has an effect in preneoplastic lesions in the peripheral airways and alveoli requires additional investigation.