A widely prescribed pain reliever may one day have value in helping to prevent lung cancer.
Researchers report that Celebrex (celecoxib), the last remaining cox-2 inhibitor on the U.S. market, may reduce levels of a biomarker indicating risk for this deadly disease. The team presented its findings Sunday at the American Society of Clinical Oncology annual meeting in Chicago.
They stressed that this doesn't mean people should start taking the drug for this reason, as Celebrex has noted cardiovascular side effects, albeit effects that were not seen in this short-term study.
"This is a very early study," said Dr. Shakun Malik, director of the lung cancer program at Georgetown's Lombardi Cancer Center, in Washington, D.C. "It hasn't shown any effect on actual lung cancer. All it is showing is that it affects biomarkers. The hypothesis is that if biomarkers are affected, it will help, but we haven't shown that as of yet."
The researchers agreed.
"We cannot sit here and say that taking celecoxib is going to prevent lung cancer," said study author Dr. Edward S. Kim, M.D., an assistant professor of thoracic head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston. "What we do know was that Celebrex, when taken over a three- or six-month period, was safe to administer even at a higher dose of 800 milligrams daily."
"We certainly need to move forward with prospective validation," added Kim, who spoke at a Sunday news conference. In particular, researchers need to verify if reductions in biomarkers actually translate into a reduction in the risk of developing malignancies in the lung.
"It's too early to tell, but we're definitely interested in other trials to see how they make out with survival,' said Dr. Karen Reckamp, an assistant professor of medicine at City of Hope Cancer Center in Duarte, Calif.
Lung cancer is a notoriously difficult-to-treat disease, largely because it's usually not caught in its early stages.
"Lung cancer is an extraordinarily challenging tumor type," confirmed Dr. Howard Sandler, moderator of the news conference and a professor of radiation oncology and urology at the University of Michigan.
Prevention, therefore, becomes key. Quitting smoking or never smoking, of course, greatly reduces the risk for this disease. But there are people who beat the odds even if they smoke, just as there are nonsmokers who do develop lung cancer.
"We need to continue to refine what a high-risk population is, both clinical and biological characteristics, and that leads us into biomarkers," Kim said. The researchers were primarily interested in how Celebrex might affect Ki-67, a protein that may be related to cell proliferation.
The cox-2 enzyme is expressed in both precancerous lesions in lung tissue, as well as in lung cancer, and it has an inflammatory aspect that can stimulate more cell growth within the lung.
This study involved more than 200 patients, all of whom had a history (current or prior) of a greater than 20-pack-years cigarette habit. All participants underwent biopsies at the opening of the study, at three months and again at six months.
They were then randomized to take either Celebrex or a placebo for three months, after which they either continued on that course or switched to the other arm.
Over three months, high-dose Celebrex (400 milligrams twice a day) did reduce expression levels of Ki-67, as well as the cox-2 enzyme and a third biomarker, NF-kappa-B.
The effect was seen in both current and former smokers but was stronger in current smokers, Kim said.
No cardiac side effects were seen in the group, although previous research showed a benefit to Celebrex in reducing colon cancer but, at the same time, a significant increase in adverse events.
Kim hopes that future studies will identify patients at higher risk for heart problems (the greatest risk factor is age), and take that into account. It's also unclear at this point how long individuals should take Celebrex.
As for patients who already have the disease, Kim said, "I hope we can keep you alive until you have a heart attack, because that means we have treated your lung cancer very well."
Another study also presented at the meeting found that PET/CT (positron emission tomography/computed tomography) imaging more accurately staged lung cancer cases, sparing more patients from inappropriate surgery.
PET imaging identified 14 percent of patients who had cancer too advanced for surgery, while conventional work-ups only identified 7 percent of such patients for whom surgery would have been inappropriate.