Randomized phase II trial of sulindac for lung cancer chemoprevention.

Author(s): Limburg PJ,  Mandrekar SJ,  Aubry MC,  Ziegler KL,  Zhang J,  Yi JE,  Henry M,  Tazelaar HD,  Lam S,  McWilliams A,  Midthun DE,  Edell ES,  Rickman OB,  Mazzone P,  Tockman M,  Beamis JF,  Lamb C,  Simoff M,  Loprinzi C,  Szabo E,  Jett J,  Cancer Prevention Network

Journal: Lung Cancer

Date: 2013 Mar

Major Program(s) or Research Group(s): CONSORTIA, LUACRG

PubMed ID: 23261228

PMC ID: PMC3566344

Abstract: INTRODUCTION: 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.