title: Randomized phase II trial of sulindac for lung cancer chemoprevention.
abstract: BACKGROUND
  Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (≥30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN).
  
  
  METHODS
  At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150mg bid or an identical placebo bid for 6 months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index.
  
  
  RESULTS
  Slower than anticipated recruitment led to trial closure after randomizing participants (n=31 and n=30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p=0.0005) and sulindac (30 versus 10; p=0.0003) arms, but the difference between arms was not statistically significant (p=0.92).
  
  
  CONCLUSIONS
  Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.
authors.affiliation: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. limburg.paul@mayo.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Sumithra J
authors.initials: SJ
authors.lastname: Mandrekar
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Aubry
authors.forename: Katie L Allen
authors.initials: KL
authors.lastname: Ziegler
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Yi
authors.forename: Michael
authors.initials: M
authors.lastname: Henry
authors.forename: Henry D
authors.initials: HD
authors.lastname: Tazelaar
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: Annette
authors.initials: A
authors.lastname: McWilliams
authors.forename: David E
authors.initials: DE
authors.lastname: Midthun
authors.forename: Eric S
authors.initials: ES
authors.lastname: Edell
authors.forename: Otis B
authors.initials: OB
authors.lastname: Rickman
authors.forename: Peter
authors.initials: P
authors.lastname: Mazzone
authors.forename: Melvyn
authors.initials: M
authors.lastname: Tockman
authors.forename: John F
authors.initials: JF
authors.lastname: Beamis
authors.forename: Carla
authors.initials: C
authors.lastname: Lamb
authors.forename: Michael
authors.initials: M
authors.lastname: Simoff
authors.forename: Charles
authors.initials: C
authors.lastname: Loprinzi
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
authors.forename: James
authors.initials: J
authors.lastname: Jett
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000503:physiopathology / Q000517:prevention & control*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D018890:Chemoprevention / Q000379:methods; D005260:Female; D006801:Humans; D058025:Interdisciplinary Studies; D008175:Lung Neoplasms / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012907:Smoking; D013467:Sulindac / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D013467:Sulindac