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ASCO chief unveils policy on averting lung cancer

Men and women at highest risk for lung cancer are former smokers who have been cured of the disease. That's the word from Paul A. Bunn Jr., M.D., president, American Society of Clinical Oncology, and director, University of Colorado Cancer Center, speaking at a special ASCO media event on new strategies to prevent lung cancer and other common cancers, held recently in New York City.

"Studies show there's a high risk of a second cancer because the patients' susceptibility genes make them more vulnerable. Thus, 10 years after being cured of one cancer, half the patients return with another," Bunn reported.

Investigators worldwide are looking at chemopreventive agents to see whether they deter lung cancer development in former smokers, Bunn said. Laboratory studies show that lung cancer starts with atypical cells—noted by sputum cytology—then progresses to severe dysplasia and on to cancer cells. "Six years after atypical cells are first seen, 20% of patients develop lung cancer," he explained. "Now we need large clinical trials of several promising new drugs to show whether they can help patients and prevent cancer."

But what Bunn called "a huge controversy at the Food & Drug Administration level" has erupted over when to approve certain agents for such prevention studies. The most controversial is Iressa (gefitinib, AstraZeneca), an epidermal growth factor receptor inhibitor, the safety of which some researchers have questioned. At press time, the FDA approved Iressa for the treatment of lung cancer but did not address the issue of prevention.

Earlier, the FDA ruled that gefitinib is not safe enough for large-scale chemoprevention studies—a decision Bunn opposes. "In preliminary prevention trials, gefitinib's been given to 40,000 subjects throughout the world," the ASCO chief said. "It's been found as safe as any chemotherapeutic agent, safer than many, in fact. If the FDA decision sticks, it could set back chemoprevention by decades."

But Warren Lakoff, director of pharmacy, Long Island College Hospital, who was asked to comment in an interview, disagreed: "If the FDA is uncomfortable with the design of a study, or the data, it has every right to delay approval until its questions are answered."

The ideal chemopreventive agent is safe, effective, inexpensive, and easy to take, according to ASCO literature. Several other agents in different stages of assessment as possible lung cancer blockers were discussed at the media event. These include:

• Budesonide, a steroid used to treat asthma, is being looked at in humans in the form of a spray to reach lung tissue directly and halt the progression of precancerous lesions.

• Regular aspirin use was recently associated with reduced lung cancer risk in studies, regardless of smoking status; among smokers the risk reduction was strongest in light smokers.

• A trial of celecoxib (Celebrex, Pfizer), begun in 2001 to see whether it could reduce lung cancer risk in heavy smokers, is still ongoing.

On the other hand, Bernard Levin, M.D., VP for cancer prevention, M. D. Anderson Cancer Center, remarked, "We should remember that studies assessing the value of beta-carotene not only failed to demonstrate any protective effect but showed it increased lung cancer incidence in smokers. "Likewise, there were no proven benefits for alpha- tocopherol, retinal, retinyl palmitate, N-acetylcysteine, or isotretinoin," he said.

Bunn stressed the urgency of making smoking cessation a top issue again. "Many people think we Americans are making great strides in stopping smoking. Guess again. More people are smoking now than a decade ago. And the percentage of teenagers smoking is higher than that of adults," he said. ASCO has developed a tough new tobacco policy, he stated. For example, the organization will fight to raise the price of cigarettes out of the reach of most teenagers. And ASCO will challenge the U.S. government to regulate carcinogens in tobacco smoke.

"The most powerful carcinogen for adenocarcinoma is nitrosamine. In Europe, governments strictly regulate nitrosamines in tobacco products—but not here. We have no such regulations," Bunn said.

The new, more rigorous tobacco policy will be a major focus at ASCO's annual meeting in Chicago, May 31-June 3, 2003.

Naomi Pfeiffer

The author is a clinical writer based in New York.

Naomi PFEIFFER. ASCO chief unveils policy on averting lung cancer.

Drug Topics

May 19, 2003;147:HSE11.