Uncertainty Still Surrounds Use of Vitamin A in Lung Cancer
In a major clinical trial exploring treatment of stage I non-small-cell lung cancer, the vitamin-A-type drug isotretinoin failed to protect patients from developing more tumors in the lungs and upper airways. The trial results were reported in the April 18, 2001, issue of the Journal of the National Cancer Institute.
In previous initial studies, isotretinoin (also known as Accutane®) prevented patients with cancers of the mouth, nose and upper airways (head and neck cancers) from getting a second cancer either in these areas or in the lungs. Researchers wondered whether a similar benefit would occur in patients with non-small-cell lung cancer, who have a high rate of second primary tumors (SPTs). Scott Lippman, M.D., of the University of Texas M. D. Anderson Cancer Center, in collaboration with co-investigators at many institutions, conducted a study to find out.
The researchers enrolled 1,116 patients who had had surgical treatment for non-small cell lung cancer but appeared currently free of the disease. The average age of the patients, who were mostly male and white, was 65 years old. Patients were randomly assigned to receive either 30 mg of isotretinoin or a placebo, to be taken by mouth once a day for three years. Both groups included a balanced mix of patients in terms of their smoking history as well as their type of tumor.
The patients were checked regularly with a variety of tests, including chest x-rays, to see if new SPTs had developed. On average, patients who were still living were followed up for 3.5 years. In the end, the researchers found no significant difference between the two groups in terms of SPT recurrence, how soon SPTs appeared, or overall risk of death.
However, though the trial was not designed to study smoking as a factor per se, further analysis of the data suggested that isotretinoin was actually harmful to current smokers while showing some benefit to those who had never smoked. The authors said this points to the need for a randomized trial to determine whether isotretinoin might help prevent SPTs in lung cancer patients who had quit smoking or who had never smoked.
Isotretinoin's side effects proved somewhat difficult for patients, and included lip and skin dryness, eye inflammation, and joint pain. At the end of three years, 40 percent of those receiving isotretinoin and 25 percent of the placebo group were not taking their pills as instructed.
Nearly 170,000 cases of lung cancer will be diagnosed in the United States in 2001 and more than 150,000 people will die from this disease. Approximately 75 percent of these cases will be non-small cell lung cancer, but less than one-quarter will be diagnosed at an early stage. Therefore, it's important to find effective means of preventing lung cancer, understanding that the single greatest risk factor for its development is smoking.
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