A randomized double-blind study of the biological effects of celecoxib as a chemopreventive agent in current and former smokers

1501 Background: Cyclooxygenase-2 (COX-2) is overexpressed in bronchial premalignancy and promotes tumor cell proliferation and survival. Bronchial premalignant lesions have enhanced cellular proliferation as measured by nuclear Ki-67 expression. In histologically normal bronchial epithelium, Ki-67 is detectable in basal and parabasal layers. Celecoxib (COX-2 inhibitor) may have activity in the bronchial epithelium of current and former smokers and this was tested by measuring Ki-67 in bronchial biopsy samples. Methods: Patients (pts) with or without a prior cancer history were required to have at least a 20 pack-year smoking history and be disease-free for at least 6 months (mos). Pts were randomized into one of 4 treatments (3-mo intervals): celecoxib then placebo; celecoxib then celecoxib; placebo then celecoxib; placebo then placebo. Pts underwent bronchoscopy with biopsies at baseline, 3 and 6 mos. Celecoxib was administered at 200 mg bid (low dose, 81 pts), then changed to high-dose (400 mg bid, 123...