Researchers from M.D. Anderson Cancer Center in Houston reported Sunday that high doses of the arthritis medication Celebrex might prevent lung cancer in heavy smokers. The drug works by inhibiting the COX-2 enzyme that causes inflammation, which has been linked to cancer.
The researchers studied 212 heavy smokers and discovered that those who took a high dose of Celebrex, also known as celecoxib, had less of a certain type of precancerous lung cell changes compared with those who took placebo.
None of those who participated in the study had any heart-related problems such as those with Merck & Co Inc’s arthritis drug Vioxx, a COX-2 inhibitor that was later withdrawn from the market.
“Celebrex was safe and we did not see any cardiovascular events,” said Dr. Edward Kim of M.D. Anderson Cancer Center in Houston, while presenting his research at a meeting of the American Society of Clinical Oncology in Chicago.
Dr. Kim said the study suggests that a high dose of Celebrex might interfere with the cellular changes that precede lung cancer. However, the findings are preliminary and need confirmation by larger, longer studies.
“This is not a study where we go tell someone who is a heavy smoker to start taking Celebrex to prevent lung cancer,” Dr. Kim said in a Reuters interview.
Although the study began prior to news in September 2004 that Vioxx doubled the risk of stroke and heart attack in some patients, Dr. Kim said it was put on hold in December 2004 at the request from the National Cancer Institute (NCI), which funded the trial, and Pfizer, in order to give researchers time to look for signs of heart attacks or strokes.
The work resumed again in May 2005 after researchers added safeguards to reduce heart risks, which included consultations with cardiologists.
Dr. Kim said the researchers were looking for early changes in the body that might indicate the drug could reduce the chances of developing lung cancer, rather than a direct measure of cancer prevention that could take many years.
Indeed, two large, long-term studies on lung cancer prevention with beta-carotene and vitamin A supplements found they actually increased the risk of developing lung cancer.
“We have not had positive results with these studies. Now we would like to search for an intermediate endpoint or biomarker,” said Dr. Kim during a media briefing.
“Perhaps that will lead us in the direction of who we need to target in the future,” he said.
Dr. Kim said the researchers chose to study Celebrex because previous research conducted in cells, mice and people found that the COX-2 enzyme is present at higher than normal levels in lung cancer and in precancerous lesions of the lung. COX-2 is believed to play a part in the development of blood vessels that feed tumors.
In the study, Dr. Kim measured levels of the protein Ki-67, a marker for cell growth. They wanted to determine if Celebrex affected levels of this protein in tissue samples taken from the lungs of heavy smokers.
The researchers began by obtaining lung samples from six predetermined areas of the lung. Then the study participants received either a 200-milligram or a 400-milligram dose of Celebrex twice a day, or a placebo. Samples were obtained again at three-month and six-month intervals. The researchers found that the group receiving the higher dose of Celebrex realized a reduction in Ki-67 protein levels. Dr. Kim added that it would be important to find better ways of identifying those at highest risk for lung cancer for whom the benefits high-dose COX-2 inhibitor would outweigh the risks.
According to the American Cancer Society, lung cancer is the leading cause of cancer death in the United States. About 215,000 people will be diagnosed with lung cancer this year, and about 114,000 people will die from the disease.
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