• 8/26/2006
  • Chicago, IL
  • John Otrompke
  • www.docguide.com

Researchers who are evaluating the safety of pioglitazone in nondiabetic patients with precancerous leukoplakia say the drug can be delivered safely for 90 days to non-diabetic people with oral leukoplakia.

Nelson Rhodus, MD, professor of oral medicine, department of diagnostic and biological sciences, University of Minnesota, Minneapolis, Minnesota, and colleagues conducted a phase 2a trial to evaluate the safety of pioglitazone in nondiabetic patients with high-risk oropharyngeal leukoplagia. Their findings were presented in a poster session here at the 2006 annual meeting of the American Head and Neck Society (AHNS).

Leukoplakia is a precancerous oral condition which affects 1% of the U.S. adult population. Individuals with the condition are at relatively high-risk for conversion to malignancy, with 5% of those with leukoplakia going on to develop oral cancer. By comparison, 1% of those with colonic polyps go on to develop intestinal cancer, the poster said.

The researchers undertook this study because the thiazolidinedione class of drugs, commonly used for treatment of type 2 diabetes, bind to peroxisome proliferating-activated receptor (PPAR) gamma nuclear receptors and are therefore theorized to drive dysplastic cells to decrease proliferation and increase maturation.

The trial enrolled patients with precancerous leukoplakia but no oral cancer, diabetes, prior radiation to the oral cavity, or serious oral infections between January of 2004 and March of 2006.

All patients received 45 mg daily of pioglitazone for 12 weeks. Researchers evaluated laboratory abnormalities using paired Student’s t-test and clinical side effects using National Cancer Institute Common Toxicity Criteria version 3.

After 12 weeks of treatment, 1 patient (5.5%) experienced idiopathic peripheral edema of the lower extremity and underwent dose reduction to 30 mg daily. There were no other treatment-related side effects, according to the abstract, which is a similar rate as the 7% rate seen among diabetics reported in the literature, according to the abstract.

The researchers observed a 10% decrease in blood lymphocyte counts — 31.1% pre-treatment; 27.9% post-treatment (P < .025) — which was not significant. There was also a decrease in absolute lymphocyte counts from 2.24 to 1.96 (P = .02) which fall within the normal range, according to the researchers.

The authors theorized that the lymphocyte effects may be related to the anti-inflammatory effects of this class of drugs.

“We conclude that 45 mg daily of pioglitazone can be delivered safely for 90 days to non-diabetic people with oral leukoplakia in a phase 2 clinical trial setting,” the authors stated in their poster.

Source:
Presentation title: Safety of PPAR Gamma Activation Strategies for Precancerous Leukoplakia – AHNS