A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with dysplasia of the bronchial epithelium.
OBJECTIVE
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.


METHODS
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 microg 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 BclII 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 microg 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 BclII 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.
Lam
Stephen
S
Department of Respiratory Medicine, British Columbia Cancer Agency and the University of British Columbia, Vancouver, British Columbia, Canada. slam@bccancer.bc.ca
leRiche
Jean C
JC
McWilliams
Annette
A
Macaulay
Calum
C
Dyachkova
Yulia
Y
Szabo
Eva
E
Mayo
John
J
Schellenberg
Robert
R
Coldman
Andy
A
Hawk
Ernest
E
Gazdar
Adi
A
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001706:Biopsy; D001980:Bronchi / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use*; D003371:Cough / Q000139:chemically induced; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010614:Pharynx / Q000187:drug effects / Q000473:pathology; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D020545:Respiratory Mucosa / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D001993:Bronchodilator Agents; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019819:Budesonide