Randomized phase II trial of sulindac for lung cancer chemoprevention

Paul J. Limburg; Sumithra J. Mandrekar; Marie Christine Aubry; Katie L.Allen Ziegler; Jun Zhang; Joanne E. Yi; Michael Henry; Henry D. Tazelaar; Stephen Lam; Annette McWilliams; David E. Midthun; Eric S. Edell; Otis B. Rickman; Peter Mazzone; Melvyn Tockman; John F. Beamis; Carla Lamb; Michael Simoff; Charles Loprinzi; Eva Szabo; James Jett

doi:10.1016/j.lungcan.2012.11.011

Randomized phase II trial of sulindac for lung cancer chemoprevention

Paul J. Limburg, Sumithra J. Mandrekar, Marie Christine Aubry, Katie L.Allen Ziegler, Jun Zhang, Joanne E. Yi, Michael Henry, Henry D. Tazelaar, Stephen Lam, Annette McWilliams, David E. Midthun, Eric S. Edell, Otis B. Rickman, Peter Mazzone, Melvyn Tockman, John F. Beamis, Carla Lamb, Michael Simoff, Charles Loprinzi, Eva SzaboJames Jett

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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 150. mg 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 150. mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.

Original language	English (US)
Pages (from-to)	254-261
Number of pages	8
Journal	Lung Cancer
Volume	79
Issue number	3
DOIs	https://doi.org/10.1016/j.lungcan.2012.11.011
State	Published - Mar 2013

Keywords

Chemoprevention
Lung cancer
NSAIDs
Phase II clinical trial
Sulindac

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

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10.1016/j.lungcan.2012.11.011

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Limburg, P. J., Mandrekar, S. J., Aubry, M. C., Ziegler, K. L. A., Zhang, J., Yi, J. E., Henry, M., Tazelaar, H. D., Lam, S., McWilliams, A., Midthun, D. E., Edell, E. S., Rickman, O. B., Mazzone, P., Tockman, M., Beamis, J. F., Lamb, C., Simoff, M., Loprinzi, C., ... Jett, J. (2013). Randomized phase II trial of sulindac for lung cancer chemoprevention. Lung Cancer, 79(3), 254-261. https://doi.org/10.1016/j.lungcan.2012.11.011

Limburg, PJ , Mandrekar, SJ, Aubry, MC, Ziegler, KLA, 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 2013, 'Randomized phase II trial of sulindac for lung cancer chemoprevention', Lung Cancer, vol. 79, no. 3, pp. 254-261. https://doi.org/10.1016/j.lungcan.2012.11.011

@article{fd2175a7f7434dc384f72b81521d43bc,

title = "Randomized phase II trial of sulindac for lung cancer chemoprevention",

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 150. mg 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 150. mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.",

keywords = "Chemoprevention, Lung cancer, NSAIDs, Phase II clinical trial, Sulindac",

author = "Limburg, {Paul J.} and Mandrekar, {Sumithra J.} and Aubry, {Marie Christine} and Ziegler, {Katie L.Allen} and Jun Zhang and Yi, {Joanne E.} and Michael Henry and Tazelaar, {Henry D.} and Stephen Lam and Annette McWilliams and Midthun, {David E.} and Edell, {Eric S.} and Rickman, {Otis B.} and Peter Mazzone and Melvyn Tockman and Beamis, {John F.} and Carla Lamb and Michael Simoff and Charles Loprinzi and Eva Szabo and James Jett",

note = "Funding Information: The authors gratefully acknowledge the staff of the Mayo Clinic Clinical Research Unit (supported by grant M01-RR00585 ); Dr. Wilma Lingle, Cindy Fitting, Maria Resner, Colleen Garvey, and Sharon Kaufman for their assistance with study design, administration and manuscript preparation. This work was sponsored by the National Cancer Institute, Division of Cancer Prevention , contract N01-CN-35000.",

year = "2013",

month = mar,

doi = "10.1016/j.lungcan.2012.11.011",

language = "English (US)",

volume = "79",

pages = "254--261",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "3",

}

TY - JOUR

T1 - Randomized phase II trial of sulindac for lung cancer chemoprevention

AU - Limburg, Paul J.

AU - Mandrekar, Sumithra J.

AU - Aubry, Marie Christine

AU - Ziegler, Katie L.Allen

AU - Zhang, Jun

AU - Yi, Joanne E.

AU - Henry, Michael

AU - Tazelaar, Henry D.

AU - Lam, Stephen

AU - McWilliams, Annette

AU - Midthun, David E.

AU - Edell, Eric S.

AU - Rickman, Otis B.

AU - Mazzone, Peter

AU - Tockman, Melvyn

AU - Beamis, John F.

AU - Lamb, Carla

AU - Simoff, Michael

AU - Loprinzi, Charles

AU - Szabo, Eva

AU - Jett, James

N1 - Funding Information: The authors gratefully acknowledge the staff of the Mayo Clinic Clinical Research Unit (supported by grant M01-RR00585 ); Dr. Wilma Lingle, Cindy Fitting, Maria Resner, Colleen Garvey, and Sharon Kaufman for their assistance with study design, administration and manuscript preparation. This work was sponsored by the National Cancer Institute, Division of Cancer Prevention , contract N01-CN-35000.

PY - 2013/3

Y1 - 2013/3

N2 - 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 150. mg 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 150. mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.

AB - 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 150. mg 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 150. mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.

KW - Chemoprevention

KW - Lung cancer

KW - NSAIDs

KW - Phase II clinical trial

KW - Sulindac

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JF - Lung Cancer

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ER -

Randomized phase II trial of sulindac for lung cancer chemoprevention

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