Pioglitazone, a drug used to treat type 2 diabetes, is the focus of a clinical trial under the leadership of Frank Ondrey, MD, PhD, associate professor, Otolaryngology, University of Minnesota, and Jay Boyle, MD, director, Fellowship Training Program, Memorial Sloan-Kettering Cancer Center. This Phase IIB randomized, placebo-controlled trial is an inter-consortium collaborative study for oral premalignant lesions, and is supported by the National Cancer Institute.
Head and neck cancers affect more than 38,000 individuals in the United States every year, and more than 11,000 men and women die annually from these cancer types. In this trial, researchers are investigating interventions to stop the progression of oral leukoplakia, the persistent sores or white patches in the mouth that often precede oral cancer. According to Ondrey, about 5 percent of patients with oral leukoplakia develop invasive cancer over the course of five years.
Oral leukoplakia lesions can be the result of smoking or chewing tobacco, long-term alcohol use, excessive sun exposure to the lips and chronic irritation of the mucous membranes in the mouth. Mouth cancer can occur on the lips, gums, tongue, inside lining of the cheeks or the roof and floor of the mouth. It is one of several cancers under the umbrella category of head and neck cancers. Symptoms of mouth cancer can include:
- A sore that doesn't heal
- A lump or thickening of the skin or lining of the mouth
- A white or reddish patch on the inside of the mouth
- Loose teeth or poorly fitting dentures
- Tongue pain
- Jaw pain or stiffness
- Difficult or painful chewing or swallowing
- Sore throat
- A feeling that something is caught in the throat
Pioglitazone is an FDA-approved oral antidiabetic drug in the class of thiazolidinediones that have been shown to inhibit growth of some epithelial cancer cells. It is commonly used to lower blood sugar in patients with diabetes and is designed to target a protein that may change how genes affect the body’s metabolism. In the case of mouth cancer, pioglitazone appears to activate nuclear receptors and alter the expression of genes affecting cell growth, cell differentiation and cell death.
In the clinical trial currently underway, patients with oral leukoplakia are randomly assigned to receive either pioglitazone or a placebo daily for six months. Physicians measure the ability of the drug to shrink or eliminate leukoplakia lesions in the mouth and reduce the amount of dysplasia or hyperplasia associated with them.
A previous study, led by Ondrey from 2004 to 2008, found that three months of pioglitazone eliminated most of the lesions, but not the dysplasia. “We felt the study provided strong evidence that pioglitazone may be effective as a chemoprevention drug, so our next step was this randomized, placebo-controlled study that will treat patients for six months instead of three in the hopes of further reducing both the leukoplakia lesions as well as the dysplasia,” Ondrey said.
Patients interested in the current trial must have a suspected or histologically confirmed index oral premalignant lesion of 8 mm or greater in length and a width of 3 mm or greater. Potential participants must be 18 years old and not using any other oral cancer chemopreventive therapy. Women who are pregnant or nursing are not eligible. Anyone of childbearing potential (including men) must use contraception during the study. A baseline EKG must not show signs of acute cardiac ischemia or dysrhythmia. The patient must not have congestive heart failure (CHF) or a history of CHF, evidence of liver disease, diabetes, a history of colorectal or bladder cancer or any other invasive cancer within the past 18 months.
“Our goal is to learn how pioglitazone might affect oral premalignant lesions and reduce the risk of mouth cancer,” said Ondrey. “At the same time, we will study the safety of the drug itself.”
For more information on the study, please contact the cancer information line nurse at 612-624-2620 or study coordinator Beverly Wuertz at 612-625-3090.