Laird Harrison

March 23, 2011

March 23, 2011 (San Diego, California) — In a phase 2 clinical trial, the thiazolidinedione pioglitazone partially or completely eliminated two thirds of leukoplakia lesions, which can sometimes become cancerous, researchers reported here at the International Association of Dental Research 89th General Session and Exhibition.

Pioglitazone (Actos, Takeda Pharmaceuticals) "works pretty well — better than anything we've seen before," coinvestigator Nelson Rhodus, DMD, MPH, professor of oral medicine and otolaryngology at the University of Minnesota, Minneapolis, told Medscape Medical News.

Leukoplakia lesions, which are usually caused by irritation, appear on the tongue or sometimes on the insides of the cheek. About 17% of the lesions may ultimately become invasive oral cancer, and no treatment has been shown to reliably prevent this, said Dr. Rhodus.

They researchers got interested in pioglitazone because it preserves cell differentiation, enhances apoptosis of tumor cells, and prevents tumor angiogenesis.

In a previous study, the researchers noticed a decrease in head, neck, and lung neoplasms in a population of diabetic men older than 40 years who took thiazolidinedione agents.

For this study, Dr. Rhodus and colleagues from the University of Minnesota, Minneapolis, and the National Cancer Institute in Bethesda, Maryland, recruited 21 patients with lesions, many of which were characterized histopathologically as hyperplastic or dysplastic.

The 21 patients received pioglitazone 45 mg daily for 12 weeks. Dr. Rhodus's team measured the leukoplakia lesions and took biopsies of the involved mucosa to evaluate histologic response in all participants.

They determined that 15 of the 21 patients in the pioglitazone group had a clinical and/or histologic response.

In the pioglitazone group, the lesions completely disappeared in 3 patients and partially disappeared in 12 patients, the epithelium completely returned to normal in 1 patient.

The only adverse reaction was edema, Dr. Rhodus said, and that affected 11% of the pioglitazone group.

"This is a novel finding that is distinctly better than the use of retinoids tried some time ago, which declined because of side effects," Stephen J. Challacombe, BDS, PhD, a clinical professor of oral medicine and immunology at King's College London, United Kingdom, told Medscape Medical News.

Because it is a diabetes drug, researchers checked the subjects' glucose levels, but they found no change, apparently because pioglitazone only affects glucose in diabetics, said Dr. Rhodus.

He cautioned that the results of this phase 2 trial are only preliminary; it is too small to be definitive, and there was no placebo used.

The results merit a larger clinical trial, said John S. Greenspan, BDS, PhD, from the University of California, San Francisco. "I thought it was a fascinating study, an excellent pilot/initial exploration of the safety and efficacy of pioglitazone in the management of oral leukoplakia. If confirmed in larger-scale multicenter trials, this could add an important approach to the control of that lesion."

In fact, the researchers are now undertaking a phase 2b randomized clinical trial, Dr. Rhodus reported.

If the drug is eventually approved for leukoplakia, it is unlikely that general dentists will prescribe it, he added, but they can identify the types of lesions they should refer to oral surgeons, oral pathologists, or otolaryngologists for treatment, he said.

This study was funded by the National Cancer Institute. Dr. Rhodus and Dr. Greenspan have disclosed no relevant financial relationships.

International Association of Dental Research (IADR) 89th General Session and Exhibition: Abstract 945. Presented March 17, 2011.

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