The University of Texas M. D. Anderson Cancer Center has reactivated a lung cancer chemoprevention trial studying Celecoxib, an anti-inflammatory medication also known as Celebrex.

M. D. Anderson voluntarily suspended the trial with Celebrex last December at the request of Pfizer, the maker of the drug, and the National Cancer Institute ( NCI ), the funding source for the study, until further data on the drug could be analyzed.

After suspension of the trial, further review of the data by the Food and Drug Administration ( FDA ) supported the initial concern that patients taking Celebrex were at increased risk for heart attack and stroke.

In February, advisors to the FDA recommended that Celebrex 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 the trial had been on hold for five months, the investigators re-applied to M. D. Anderson's Institutional Review Board to reactivate the trial studying the effectiveness of the anti-inflammatory for preventing lung cancer in former and current smokers.

The investigators have added stringent guidelines to reduce risk to the participants and to insure that the drug will be safe. These revised guidelines are especially important for patients with histories of hypertension or cardiovascular events.

Patients' blood pressure and lipid counts will be tracked closely for any fluctuations in those two warning signs of cardiovascular change, and patients will be aggressively treated should any change occur. In addition, individuals will be treated in the trial for only six months, half of the 12-month period in which the first signs of increased risk were observed on the colon cancer prevention studies. Excluded from participation will be individuals who have previously had heart attacks or strokes.

"At this point, there is nothing available to deter lung cancer in smokers, even in those who have quit," said Jonathan M. Kurie, principal investigator. " In looking at the data, we believe the potential benefit to the patient is greater than the risk, and we have ample safeguards in place to monitor patients even more closely than they are now. We continue to believe this drug has potential to reduce the risk of lung cancer and that is a tremendous opportunity not to be overlooked."

Celebrex is in a class of medications known as nonsteroidal anti-inflammatory drugs ( NSAIDs ), like Aspirin or Ibuprofen, which work by blocking chemical enzymes that cause inflammation. Most NSAIDs inhibit two cyclooxygenase enzymes ( Cox-1 and Cox-2 ), but since Cox-1 helps maintain the lining of the stomach, use of these pills can lead to the development of ulcers. Celebrex only inhibits Cox-2 enzyme.

Specifically, the Cox-2 enzyme inside cancer cells is thought to control the synthesis of prostaglandins, which are substances believed to trigger cancer cell growth. Researchers believe that prostaglandins promote the growth of new blood vessels to feed tumors, and also protect new cancers from destruction by the body's immune system. Blocking the Cox-2 enzyme may reduce the amount of prostaglandin available to cancer cells and thus repress tumor growth, says Kurie.

"Lab studies have shown that Cox-2 is expressed at a high level in lung cancer," he says. "They may be triggering inflammation which we suspect plays a role in lung cancer.

The trial has been open since 2003 with the goal of enrolling 200 former and current smokers. The trial is about two-thirds complete, said Kurie.

In addition to plans to continue the recruitment of new participants, those participants who enrolled prior to the suspension of the trial will be given the opportunity to re-enroll so the full protocol can be completed. Participants on the trial will receive a diagnostic bronchoscopy, among other outpatient tests, at the beginning, middle and end of the study.

Lung cancer is the leading cause of cancer mortality in men and women, accounting for 28 percent of all cancer deaths in the United States, according to the American Cancer Society. There are about 173,000 new cases of lung cancer diagnosed in this country and an estimated 157,000 people died of the disease in 2004. About 90 percent of lung cancer occurs in current smokers or former smokers, said Kurie.

Source: University of Texas M. D. Anderson Cancer Center, 2005


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