Trial Uses Vitamin A To Prevent Lung Cancer in Former Smokers

 HOUSTON—There are currently 581 clinical trials underway at The University of Texas M.D. Anderson Cancer Center, John Mendelsohn, MD, the Center’s president, said at a seminar held in conjunction with the opening of the Center’s new Alkek Hospital .

Most protocols are treatment trials, Dr. Mendelsohn said, but one groundbreaking study is a prevention trial aimed at lung cancer, using retinoic acid, a form of vitamin A.

Jonathan M. Kurie, MD, of the Department of Thoracic/Head and Neck Medical Oncology, is leading the study. “The relative lack of success we have had in the treatment of established lung cancer points us toward intervening at earlier stages of the disease,” he said.

The best prevention strategy for smokers—quitting—is obvious, but this answer “is not so simple,” Dr. Kurie said. “Now, over 50% of all lung cancers occur in people who have quit smoking.” Recent reports show that former smokers have an increased risk of developing lung cancer even up to 30 years after stopping.

Early clinical trials of retinoic acid in the 1980s showed a reduced incidence of second cancers in patients who had undergone resection of a head and neck cancer. The new trial, being conducted by Dr. Kurie and colleagues at M.D. Anderson and the University of Texas Southwestern Medical Center at Dallas, targets former smokers.

“We are trying to answer several questions,” he said. “First, we want to learn to identify individuals in the population of former smokers who are at increased lung cancer risk.” Toward this end, Drs. Margaret Spitz, Walter Hittelman, and Li Mao are trying to identify two kinds of genes—genes that, if inherited, confer increased lung cancer risk and genes that, if damaged by cigarette smoke, lead to the development of lung cancer.

The second trial objective is to test the effectiveness of different vitamin-A-related drugs in repairing the damage caused by previous smoking. Potential benefits for participants include early detection of a potentially cancerous condition and possible reduction of DNA-damaged cells.

Each study participant undergoes bronchoscopy and biopsy at six predetermined sites inside the lung. These samples are then studied for evidence of damage to the chromosomes known to be damaged by lung cancer (3P, 9P, 17P). “We’re looking at those areas for evidence of change so we can quantitatively assess the amount of damage,” Dr. Kurie said.

Participants are then randomized to receive a placebo or retinoic acid. After treatment for 3 months, a second bronchoscopy and repeat biopsies are performed. “Again,” Dr. Kurie said, “we get a quantitative measure of the damage, so that we will be able to determine whether the treatment had any effect.”

To date, the study has shown that more than 50% of participants, all former smokers, have “a tremendous amount of DNA damage,” Dr. Kurie said. He called the study “groundbreaking, since no one has ever shown this sort of damage before in former smokers. We were absolutely astounded at what we saw. I think the problem is much more profound than we thought.”

People who have successfully stopped smoking are being sought for this ongoing trial. Contact the Research Nurse, Department of Thoracic/Head & Neck Medical Oncology, (713) 745-2784.