A new study by Jenny Mao, professor of medicine at the University of New Mexico, and colleagues at UCLA suggests that Celebrex, a common anti-inflammatory drug used to treat arthritis and other diseases, may prevent lung cancer in former smokers. Published in the July issue of the scientific journal Cancer Prevention Research, the study found that Celebrex – or Celecoxib, as it is known generically – decreased cell proliferation in the air passages of former heavy smokers.
Such cell proliferation may contribute to the development of lung cancer. Study participants who received Celebrex for six months showed a 34 percent average decrease in a biomarker for cell proliferation, as well as other bronchial benefits. While still preliminary, the results warrant further investigation in a larger clinical trial.
"These findings are very exciting," said Mao, chief and professor of medicine at the New Mexico VA Health Care System and member of the UNM Cancer Center. "There are 45 million former smokers in the US. These individuals have already significantly lowered their lung cancer risk by following medical advice and quitting, but they still have an elevated level of risk. Researchers have been working hard to find ways to reduce lung cancer risk in this group. Our latest study provides further evidence to support the continued evaluation of Celebrex for lung cancer chemoprevention in these high-risk individuals."
Lung cancer is the leading cause of cancer-related death in the U.S. and around the world, responsible for about 1.3 million annual deaths worldwide. In the U.S., approximately 222,500 cases of lung cancer are diagnosed each year, resulting in 157,300 deaths. Most of these cases result directly from smoking. There are an estimated 45 million former smokers in the U.S. and another 45 million who currently smoke.
The best way for smokers to lower their lung cancer risk is to stop smoking. Former smokers have a lower lung cancer risk than current smokers, but remain more likely to develop the disease than people who have never smoked. In recent years, former smokers have become prime candidates for chemoprevention – the use of therapeutic agents to prevent or delay illness. The Celebrex research has produced some of the most promising results reported in lung cancer chemoprevention to date. The drug works by inhibiting COX-2, a naturally occurring enzyme that plays an important role in the development of lung tumors.
Mao and colleagues' research involved 137 patients, 101 of whom completed the study, over the age of 45 who had successfully quit smoking for at least a year after years of heavy smoking. Approximately half of the study participants were randomly assigned to take Celebrex for six months. Using baseline and six-month bronchoscopies, researchers measured the amount of a biomarker called Ki-67, a useful index of rapid cell proliferation that can set the stage for tumor development. The Celebrex group showed a 34 percent average decrease in Ki-67, whereas the placebo group saw a 3.8 percent increase. Significantly, the decreases in the Celebrex group also correlated with reductions in lung nodules, a potential precursor to cancer.
The study further found a correlation between Ki-67 decreases and the expression of key metabolizing enzymes in cells retrieved from the lungs, suggesting that these enzymes could serve as a potential predictive marker of a person's responsiveness to Celebrex. This finding establishes an important first step toward personalizing lung cancer prevention.
The success of the current study paves the way for a much larger phase three clinical trial, which is necessary to validate results and help researchers better understand side effects. Celebrex is already known to increase the risk of cardiovascular disease. Researchers therefore caution that patients who have significant cardiovascular risk factors, other than smoking, are not candidates for the drug.