Biological activity of celecoxib in the bronchial epithelium of current and former smokers.
Non-small cell lung cancer is the primary cause of cancer-related death in Western countries. One important approach taken to address this problem is the development of effective chemoprevention strategies. In this study, we examined whether the cyclooxygenase-2 inhibitor celecoxib, as evidenced by decreased cell proliferation, is biologically active in the bronchial epithelium of current and former smokers. Current or former smokers with at least a 20 pack-year (pack-year = number of packs of cigarettes per day times number of years smoked) smoking history were randomized into one of four treatment arms (3-month intervals of celecoxib then placebo, celecoxib then celecoxib, placebo then celecoxib, or placebo then placebo) and underwent bronchoscopies with biopsies at baseline, 3 months, and 6 months. The 204 patients were primarily (79.4%) current smokers: 81 received either low-dose celecoxib or placebo and 123 received either high-dose celecoxib or placebo. Celecoxib was originally administered orally at 200 mg twice daily and the protocol subsequently increased the dose to 400 mg twice daily. The primary end point was change in Ki-67 labeling (from baseline to 3 months) in bronchial epithelium. No cardiac toxicities were observed in the participants. Although the effect of low-dose treatment was not significant, high-dose celecoxib decreased Ki-67 labeling by 3.85% in former smokers and by 1.10% in current smokers-a significantly greater reduction (P = 0.02) than that seen with placebo after adjusting for metaplasia and smoking status. A 3- to 6-month celecoxib regimen proved safe to administer. Celecoxib (400 mg twice daily) was biologically active in the bronchial epithelium of current and former smokers; additional studies on the efficacy of celecoxib in non-small cell lung cancer chemoprevention may be warranted.
Kim
Edward S
ES
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Hong
Waun K
WK
Lee
J Jack
JJ
Mao
Li
L
Morice
Rodolfo C
RC
Liu
Diane D
DD
Jimenez
Carlos A
CA
Eapen
Georgie A
GA
Lotan
Reuben
R
Tang
Ximing
X
Newman
Robert A
RA
Wistuba
Ignacio I
II
Kurie
Jonathan M
JM
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000517:prevention & control; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000187:drug effects*; D008175:Lung Neoplasms / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage*; D020545:Respiratory Mucosa / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib