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Lung cancer chemoprevention with celecoxib in former smokers.

Author(s): Mao JT, Roth MD, Fishbein MC, Aberle DR, Zhang ZF, Rao JY, Tashkin DP, Goodglick L, Holmes EC, Cameron RB, Dubinett SM, Elashoff R, Szabo E, Elashoff D

Affiliation(s): Pulmonary and Critical Care Section, New Mexico VA Health Care System/University of New Mexico, Albuquerque, New Mexico 87108, USA. jenny.mao@va.gov

Publication date & source: 2011-07, Cancer Prev Res (Phila)., 4(7):984-93.

Publication type: Clinical Trial, Phase II; Randomized Controlled Trial; Research Support, N.I.H., Extramural

Ample studies suggest that the cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway plays a pivotal role in carcinogenesis and that COX-2 inhibition may help prevent lung cancer. Therefore, we conducted a randomized, double-blind, placebo-controlled trial of the COX-2-selective inhibitor celecoxib (400 mg bid for 6 months) in former-smokers (age >/= 45, >/= 30 pack-years of smoking, >/= 1 year of sustained abstinence from smoking). We assessed the impact of celecoxib on cellular and molecular events associated with lung cancer pathogenesis; the primary endpoint was bronchial Ki-67 labeling index (Ki-67 LI) after 6 months of treatment. Of 137 randomized subjects, 101 completed both baseline and 6-month bronchoscopies and were evaluable for the primary endpoint analysis. The beneficial effect on Ki-67 LI was greater in the celecoxib arm (versus placebo) in a mixed-effects analysis (P = 0.0006), and celecoxib significantly decreased Ki-67 LI by an average of 34%, whereas placebo increased Ki-67 LI by an average of 3.8% (P = 0.04; t test). In participants who crossed over to the other study arm at 6 months (all of whom had received 6 months of celecoxib at the end of a 12 months treatment period), the decreases in Ki-67 LI correlated with a reduction and/or resolution of lung nodules on computed tomography. Celecoxib significantly reduced plasma c-reactive protein and interleukin-6 mRNA and protein and increased 15(S)-hydroxy-eicosatetraenoic acid levels in bronchoalveolar lavage (BAL) samples. The baseline ratio of COX-2 to 15-hydroxyprostaglandin dehydrogenase mRNA in BAL cells was a significant predictive marker of Ki-67 response to celecoxib (P = 0.002). Our collective findings support the continued investigation of celecoxib for lung cancer chemoprevention in former smokers at a low risk of cardiovascular disease.

Page last updated: 2011-12-09

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