This study is proposed based on our work showing that the diabetes drug Pioglitazone strongly
inhibits growth of tissue cultured squamous cell carcinoma (SCC) of the skin. This occurs at
concentrations readily achievable by oral administration of this drug using doses currently
approved for the treatment of diabetes. In our study, we propose to enroll 40 non-diabetic
adult subjects (18-80 yrs of age inclusive) with a documented clinical history of frequent
occurrence of skin squamous cell cancer to receive Pioglitazone (Actos®,Takeda
Pharmaceuticals). Each subject will receive usual care for all new tumors they develop while
on study (i.e, excision and plastic repair). The study protocol will randomize (1:1) patients
for 6 months of observation followed by 6 months of treatment (group 1) or 6 months of
treatment with drug followed by observation for 6 months (to examine washout effects). The
biopsy specimens collected on and off therapy will be examined to determine if they express
AKR1C3, an enzyme we believe increases resistance of SCC to prostaglandin inflammatory
mediators. We will also examine the histologic grade of the removed tumors and study whether
Pioglitazone treatment can decrease the number of aggressive versus well differentiated
tumors in study patients. This pilot study is designed to detect a statistically significant
change in SCC tumor numbers but is not sponsored by the drug manufacturer. The data obtained
will not be used to effect a change in the product label.