This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200612-1770OCv1 175/10/1061    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van den Berg, R. M. Articles by Smit, E. F. Search for Related Content PubMed PubMed Citation Articles by van den Berg, R. M. Articles by Smit, E. F.

The Influence of Fluticasone Inhalation on Markers of Carcinogenesis in Bronchial Epithelium

¹ Department of Pulmonology, VU University Medical Center (VUMC), Amsterdam, The Netherlands; ² Departments of Biometrics and ³ Thoracic Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/AvL), Amsterdam, The Netherlands; and ⁴ Department of Pathology, VU University Medical Center (VUMC), Amsterdam, The Netherlands

Correspondence and requests for reprints should be addressed to E. F. Smit, M.D., Ph.D., Department of Pulmonology, VU Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: ef.smit{at}vumc.nl

Rationale: Bronchial epithelium exposed to cigarette smoke undergoes a series of histologic changes that may ultimately lead to invasive cancer. Inhaled corticosteroids reduce the number of lung tumors developing in rats exposed to cigarette smoke.

Objectives: We studied the effect of inhaled fluticasone on premalignant lesions in smokers and patients curatively treated for head and neck cancer or lung cancer.

Methods: Participants were screened for premalignant lesions by bronchoscopy. Biopsies were taken from three to five locations and classified using WHO criteria. In case of a metaplasia index of > 15%, participants were randomized to receive a powder inhalation device containing either fluticasone 500 µg or a placebo, to be used twice a day. After 6 months, biopsies were obtained from the same locations as previously sampled. Efficacy of treatment was assessed by reversal of metaplasia/dysplasia; secondary endpoints were reversal of increased p53 and KI-67 immunoreactivity and expression of human telomerase reverse transcriptase.

Measurements and Main Results: Of the 201 subjects that were screened, 108 were included. Mean age was 53 yr (35–71), mean number of pack-years 48 (18–99), mean metaplasia index 48%, and 32% had some degree of dysplasia at baseline. The two treatment arms did not differ with respect to response or change in either metaplasia index or the expression of the markers p53, KI-67, or human telomerase reverse transcriptase.

Conclusions: Inhaled fluticasone in a dose of 500 µg twice a day does not affect the natural course of premalignant lesions in the central airways.

Key Words: cancer chemoprevention • hTERT • KI-67 • p53 • inhalational corticosteroid

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Animal studies show a chemopreventive effect of inhalational corticosteroids on lung carcinogenesis. A trial of budesonide did not find an effect on histology of bronchial premalignant lesions in humans, but did find an effect on p53 expression. What This Study Adds to the Field Inhalational corticosteroids have no effect on the natural course of premalignant bronchial lesions.

 

This article has been cited by other articles:

				S. Dubey and C. A. Powell Update in Lung Cancer 2007 Am. J. Respir. Crit. Care Med., May 1, 2008; 177(9): 941 - 946. [Full Text] [PDF]