NEW YORK, May 21 (Reuters) -- Most people remember thalidomide as the drug that caused severe birth defects in the 1960s, after it was used by pregnant women as an anti-nausea medication. Now, a study suggests a new use for the drug -- healing difficult-to-treat and painful mouth ulcers in AIDS patients. While canker sores may be merely annoying in most people, in people with AIDS the mouth ulcers can be downright dangerous, consuming large areas of the mouth and even advancing into the throat and esophagus.
According to a report in this week's issue of The New England Journal of Medicine, 55% of HIV-infected individuals who took thalidomide for four weeks had complete healing of mouth ulcers, compared with just 7% of those taking an inactive placebo drug. The drug does have some side effects, necessitating careful monitoring of the patients, according to study co-author Dr. Lawrence Fox, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
"Thalidomide appears to have great potential as a therapy for HIV-infected patients who have severe oral aphthous (shallow, painful) ulcers, but only when administered by a physician who is vigilant for possible serious side effects, including irreversible, painful peripheral nerve damage, rash and birth defects," he said in a release from the National Institutes of Health (NIH).
In the study of 57 HIV-infected patients, 29 took thalidomide, while the other 28 were given a placebo for purposes of comparison. The drug caused sleepiness or rashes in some of the patients. About half of the patients had to have the dosage reduced, and six dropped out of the four-week study because of such side effects. However, none of the patients had damage to their peripheral nerves, a known side effect of long-term thalidomide treatment. And up to 90% of patients taking the drug had at least partial healing of the mouth sores.
One disturbing finding is that thalidomide caused a small, but statistically significant increase in the amount of HIV genetic material in the blood, as well as that of tumor necrosis factor-alpha receptor type II -- two signs that the disease might be progressing.
Because of these findings, "we urge caution using thalidomide in HIV-infected persons after the two to four weeks of short-term treatment," the authors wrote. The study was conducted by the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group, a team of researchers from across the country and Puerto Rico.
"For the many patients with HIV infection who suffer from these ulcers, eating can be excruciatingly painful, which exacerbates wasting and debilitation," noted Dr. Jack Y. Killen, director of the AIDS division, in a release from the NIH. "Thalidomide is the first treatment shown in a scientific study to heal these ulcers, but the courses should be carefully monitored and limited in... duration because of the drug's potential toxicity."
If women of child-bearing age are taking the drug, they should be informed of the risk of severe birth defects, required to use effective birth control, have pregnancy tests every two weeks and there should be warnings on the labels and packages, according to the report.
"We believe this approach should be used so that women with childbearing potential can receive this treatment and other potentially beneficial therapies of known or uncertain teratogenic (birth defect causing) risk," the authors concluded.
SOURCE: The New England Journal of Medicine (1997;336:1487-1493)
