The cyclooxygenase-2 (COX-2) inhibitor celecoxib (Celebrex) appears to have potential as a powerful chemopreventive agent for lung cancer. This nonsteroidal anti-inflammatory drug (NSAID) is often prescribed to relieve the pain, tenderness, swelling, and stiffness caused by various forms arthritis.

In a report published online by Cancer Prevention Research (, Jenny T. Mao, MD, and colleagues noted that ample studies suggest the COX-2/prostaglandin E2 pathway plays a pivotal role in carcinogenesis, and that COX-2 inhibition may help prevent lung cancer. To investigate further, the team conducted a randomized, double-blind, placebo-controlled, phase II trial to explore the effects of a 6-month regimen of celecoxib 400 mg twice a day on former smokers.

The 137 participants were at least 45 years old, had at smoked for at least 30 pack-years, and had not smoked for at least 1 year. A total of 101 patients randomized to celecoxib or placebo completed both baseline and 6-month bronchoscopies and were evaluable for the primary end point analysis of bronchial Ki 67 labeling index (Ki-67 LI), a marker of cellular proliferation.

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All patients eventually underwent 6 months of celecoxib therapy by the end of a 12-month treatment period. In those who crossed groups, Ki-67 reductions correlated with a reduction and/or resolution of lung nodules on computed tomography.

Celecoxib lowered Ki-67 LI by an average of 34%, whereas placebo increased the marker by an average of 3.8%. The agent also had significant beneficial effects on other biomarkers, such as c-reactive protein and interleukin-6 mRNA.

“Taken together, these findings strongly suggest that celecoxib can be used as a chemopreventive agent in these high-risk groups,” observed Mao—pulmonary and critical care medicine section chief for the New Mexico VA Health System and a professor of medicine at the University of New Mexico, both in Albuquerque—in an announcement of the findings. She did caution, however, that large phase III trials are needed to confirm these results.

Mao’s group also specified that the investigation of celecoxib should continue in those who are at low risk for cardiovascular disease; the drug may heighten the risk of heart attack or stroke.