The influence of fluticasone inhalation on markers of carcinogenesis in bronchial epithelium

Remco M. Van Den Berg, Harm Van Tinteren, Nico Van Zandwijk, Christine Visser, Arifa Pasic, Clarissa Kooi, Thomas G. Sutedja, Paul Baas, Katrien Grünberg, Wolter J. Mooi, Peter J.F. Snijders, Pieter E. Postmus, Egbert F. Smit

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1061-1065
Number of pages5
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume175
Issue number10
DOIs
Publication statusPublished - 15 May 2007
Externally publishedYes

Keywords

  • Cancer chemoprevention
  • hTERT
  • Inhalational corticosteroid
  • KI-67
  • p53

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