ORLANDO - About half of the new cases of lung cancer diagnosed each year occur in patients who have already quit smoking. Treatment with oral doses of 9-cis-retinoic acid (9cRA), a form of vitamin A, might help protect ex-smokers from previous damage done to their lungs, said Jonathan M. Kurie, MD, Thoracic and Head and Neck Medical Oncology, M.D. Anderson Cancer Center.
At the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1177), Dr. Kurie presented data from a randomized, placebo-controlled trial showing that 9cRA significantly increased expression of the retinoic acid receptor-ß (RAR-ß) in former smokers. This effect was associated with a significant decrease in the amount of squamous metaplasia in bronchial biopsies and suggests that upregulating RAR-ß expression can, indeed, reverse some of the lung damage that leads to cancer in former smokers.
Dr. Kurie conducted this National Cancer Institute-funded study with his colleagues at M.D. Anderson, National Cancer Center Hospital, Tokyo, and Southwestern Medical Center, Dallas.
"All chemoprevention trials in current smokers have been negative or actually harmful. Beta-carotene, for example, increases conversion of procarcinogens to carcinogens in smokers," Dr. Kurie said. "These harmful effects are not seen in nonsmokers or former smokers. Since former smokers now account for 50% of lung cancers, they are an important group for trials of potentially protective agents."
Heavy smoking reduces expression of the RAR-ß receptor. Such receptor loss makes cells unresponsive to normal growth regulator signals and is associated with an increased risk of preneoplastic cellular changes. Loss of RAR-ß expression is thought to be a useful biomarker for identifying cells likely to become cancerous.
The researchers randomized 226 ex-smokers to 3 months of treatment with one of three treatments: 9cRA, 13-cis-retinoic acid (13cRA) plus alpha-tocopherol (a synthetic form of vitamin E(Drug information on vitamin e)), or placebo. All subjects had smoked at least 20 pack-years and had stopped smoking at least 12 months before the trial.
Subjects had bronchoscopic biopsies at six predetermined sites. Biopsies were done prior to treatment, after 3 months of treatment, and 3 months after the end of treatment. Biopsies were evaluated for loss of RAR-ß expression and for squamous metaplasia or dysplasia.