The anti-inflammatory medication celecoxib (Celebrex) has proven to be safe and reduces a specific proliferation measurement of precancerous lesions in the lung, according to a study from The University of Texas M. D. Anderson Cancer Center. This finding demonstrates the significance of COX-2 inhibition toward preventing lung cancer in individuals at higher risk of developing the disease. The study is the first large randomized trial of celecoxib in lung cancer prevention.

"With this study, in principal, we've been able to demonstrate the importance of COX-2 and the implications on inflammation pathway in lung cancer development," said Edward Kim, md, assistant professor in M. D. Anderson's Department of Thoracic Head and Neck Medical Oncology. "We've also been able to demonstrate that this drug class is safe and tolerable for this patient population. As we move forward in lung cancer chemoprevention, the importance of this class of drugs cannot be ignored."

Ki-67 Levels Measured
From November 2001 to September 2006, the M. D. Anderson study enrolled 212 individuals, all of whom were current or former smokers with at least a 20-pack-year smoking habit. Most participants did not have any history of cancer; however, patients with a history of cancer who had been disease-free for 6 months could participate. The median age of participants was 53. The study examined levels of Ki-67, a biomarker associated with precancerous lung lesions.

Participants underwent a baseline broncoscopy in which six predetermined biopsies were performed. They then were randomized to receive celecoxib at either 200 mg (low dose) or 400 mg (high dose) twice a day or placebo. After 3 months, participants received a second broncoscopy, the primary endpoint of the trial. Patients had the option to continue on the trial for 3 more months per their prior randomized arm; for those participants, a third and final broncoscopy was conducted at 6 months.

"In patients who had high-risk features such as smoking, especially in the current smokers, we were able to see that a higher dose of Celebrex could decrease the proliferation marker Ki-67 in these patients, as seen through their bronchial epithelium," said Kim. "We are encouraged that we have a drug like Celebrex that decreases the expression of this proliferation marker."

These findings are also significant in that the study shows that serial broncoscopies are feasible, explained Kim. "Although CT scanning and other imaging techniques are important, for lung cancer, it may be vital to examine actual tissue to see what the markers are doing in the actual epithelium of the lung so as to best understand if an individual has a higher or lower risk of developing lung cancer."

Trial Suspended, Then Resumed
In December 2004, M. D. Anderson voluntarily suspended the trial at the request of Pfizer and the National Cancer Institute (NCI), the funding source for the study, until further data on the drug's risk for cardiac toxicities, specifically heart attacks and strokes, could be investigated. Months later, advisors to the US Food and Drug Administration recommended that celecoxib continue to be studied in the treatment and prevention of cancer, and the NCI supported the continuation of the trials, encouraging investigators to weigh the risks and benefits of the drug for their specific clinical setting.

After adding stringent guidelines to further reduce the cardiac risk to patients, the M. D. Anderson investigators then reapplied to the institution's Institutional Review Board to reactivate the trial. The study reopened in May 2005.

Kim noted that there were no adverse cardiac events in the M. D. Anderson trial. Three patients experienced grade 3 toxicities on the higher dose of the drug, which were not cardiac-related.