Oral iloprost improves endobronchial dysplasia in former smokers.
Author(s): Keith RL, Blatchford PJ, Kittelson J, Minna JD, Kelly K, Massion PP, Franklin WA,
Mao J, Wilson DO, Merrick DT, Hirsch FR, Kennedy TC, Bunn PA Jr, Geraci MW,
Miller YE.
Affiliation(s): Division of Pulmonary Sciences and Critical Care Medicine, Eastern Colorado VA
Healthcare System, University of Colorado Denver, USA. robert.keith@uchsc.edu
Publication date & source: 2011, Cancer Prev Res (Phila). , 4(6):793-802
There are no established chemopreventive agents for lung cancer, the leading
cause of cancer death in the United States. Prostacyclin levels are low in lung
cancer and supplementation prevents lung cancer in preclinical models. We carried
out a multicenter double-blind, randomized, phase II placebo-controlled trial of
oral iloprost in current or former smokers with sputum cytologic atypia or
endobronchial dysplasia. Bronchoscopy was performed at study entry and after
completion of six months of therapy. Within each subject, the results were
calculated by using the average score of all biopsies (Avg), the worst biopsy
score (Max), and the dysplasia index (DI). Change in Avg was the primary end
point, evaluated in all subjects, as well as in current and former smokers. The
accrual goal of 152 subjects was reached and 125 completed both bronchoscopies
(60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age,
tobacco exposure, and baseline histology. Baseline histology was significantly
worse for current smokers (Avg 3.0) than former smokers (Avg 2.1). When compared
with placebo, former smokers receiving oral iloprost exhibited a significantly
greater improvement in Avg (0.41 units better, P = 0.010), in Max (1.10 units
better, P = 0.002), and in DI (12.45%, P = 0.006). No histologic improvement
occurred in current smokers. Oral iloprost significantly improves endobronchial
histology in former smokers and deserves further study to determine if it can
prevent the development of lung cancer.
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