Phase IIB Randomized, Placebo-Controlled Trial of Pioglitazone for Oral Premalignant Lesions: An Inter-Consortium Collaborative Study (2009-0339). See the protocol summary .
Dr. Jay Boyle, Memorial Sloan-Kettering Cancer Center, and Dr. Frank Ondrey, University of Minnesota
Drs. Jay Boyle and Frank Ondrey Principal Investigators
Why This Trial Is Important
Oral cancer is often preceded by persistent sores or white patches in the mouth known as oral leukoplakia . However, not all leukoplakia lesions progress to cancer. Although the exact causes of oral leukoplakia are unknown, they are associated with tobacco use, long-term alcohol consumption, and chronic irritation of the mucous membranes in the mouth.
Researchers are investigating several different interventions to try to stop oral leukoplakia from progressing to cancer. One promising intervention is pioglitazone (Actos), a drug that is commonly used to treat type II diabetes. In an earlier small phase II study, pioglitazone showed activity against oral leukoplakia.
“Pioglitazone acts by activating nuclear receptors and altering the expression of genes that may affect key processes in carcinogenesis, such as cell growth, cell differentiation , and cell death through apoptosis ,” said Dr. Boyle.
In this trial, patients with oral leukoplakia will be randomly assigned to receive either pioglitazone or placebo pills daily for 6 months. Doctors will assess the ability of pioglitazone to shrink or eliminate leukoplakia lesions in the mouth and reduce the degree of dysplasia or hyperplasia associated with them.
“In our previous study , we found that 3 months of treatment with pioglitazone did a good job of eliminating the lesions, but the dysplasia associated with them often didn’t change much,” said Dr. Ondrey. “We felt the study provided strong evidence that pioglitazone may be effective as a chemoprevention drug, so our next step is this randomized, placebo-controlled study that will treat patients for 6 months instead of 3 months in hopes of further reducing both the leukoplakia lesions as well as the dysplasia.”
“Pioglitazone is approved by the FDA and widely used as a diabetes drug, and it has an excellent safety profile,” added Dr. Boyle. “Given the good preliminary evidence that it might be useful as a chemopreventive and its safety record, it makes sense to further explore its use in patients with these lesions.”