Drug for Dry Mouth May Halt or Slow Cancer in Smokers

July 1, 2002

SAN FRANCISCO-The drug anethole dithiolethione (ADT)-normally used for dry mouth and marketed as Sialor or Sulfarlem-reduced the risk of new or worsening dysplastic lesions in the lungs of current and former smokers by 22%, compared with placebo, according to a study presented at a late-breaking research session of the 93rd Annual Meeting of the American Association for Cancer Research (abstract LB-119).

SAN FRANCISCO—The drug anethole dithiolethione (ADT)—normally used for dry mouth and marketed as Sialor or Sulfarlem—reduced the risk of new or worsening dysplastic lesions in the lungs of current and former smokers by 22%, compared with placebo, according to a study presented at a late-breaking research session of the 93rd Annual Meeting of the American Association for Cancer Research (abstract LB-119).

"This study shows that ADT has promise and may halt or slow the development of cancer," said Stephen Lam, MD, professor of medicine, and chair, Lung and Tumor Section, University of British Columbia.

He noted that 50% of lung cancer patients are former smokers and that even with the best smoking cessation programs, over 70% of smokers need to try quitting more than once before they succeed. "Both of these factors are why we are looking for a lung cancer chemopreventive agent," he said.

In the 6-month study, 101 current and former smokers with bronchial dysplasia were randomly assigned to receive 25 mg of ADT orally three times a day or a placebo. To qualify for the study, patients had to have smoked a pack a day for 30 years or two packs a day for 15 years. All patients had bronchial dysplasia identified by autofluorescence bronchoscopy-directed biopsies.

Risk of Progression

The risk of progression from dysplasia to cancer varies from 2% to 40% within 10 years, depending on the grade of the dysplasia, Dr. Lam said.

After completing their treatment, all patients had a repeat bronchoscopy and biopsy of the same sites, plus any new areas that looked suspicious for dysplasias. Changes in the histopathology grade of the biopsies were used as the primary endpoint biomarker.

In the lesion-specific analysis, progression of preexisting dysplastic lesions by two or more grades and/or the appearance of new lesions was 9% lower in the ADT group (8% ADT vs 17% placebo, P < .001). In the person-specific analysis, the progression rate was 22% lower in the group that received ADT (32% ADT vs 54% placebo, P = .01).

The main adverse effects of the treatment were minor gastrointestinal symptoms that resolved with dose reduction or discontinuation of the medication. "The treatment was found to be quite safe," Dr. Lam said.

He noted that the drug’s therapeutic effects in cancer are mainly based on its radical scavenger and glutathione-inducer properties.

Dr. Lam and his colleagues are planning a larger study to confirm the current findings. The next trial will consist of patients who have received curative treatment for head and neck cancer or early-stage lung cancer. In this group, the risk of recurrence rises up to 30% over 10 years. "This provides a good cancer incidence endpoint in a reasonably short time to assess the effect of ADT," Dr. Lam said.

The trial will enroll several hundred people and will take 3 to 5 years to perform. If ADT were tested as a chemopreventive in smokers, however, the trial would have to enroll more than 20,000 people and take 10 years and more than $50 million to complete. It’s simply not practical to do such a trial. "Not many people would put up that kind of money or time," Dr. Lam said.

Not FDA Approved

ADT is produced by the French company, Solvay Pharma, and is not FDA approved in the United States. It is marketed in Europe, Canada, China, and other countries, and has been sold for 30 years.

In Canada, it could conceivably be prescribed for off-label use as a chemopreventive, Dr. Lam said. "I believe ADT has promise. But with one study, the strength of evidence is not strong enough to recommend it as a standard therapy," he said.