Effects of valproic acid as a histone deacetylase inhibitor in combination with S-1 on advanced pancreatobiliary tract cancers: Clinical study phases I and II.

306 Background: Pancreatobiliary tract cancers are the most aggressive of human cancers. Histone deacetylase (HDAC) is well known to be associated with tumori-genesis through epigenetic regulation, and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We are conducting a clinical trial of combination therapy using valproic acid (VPA, a HDACI) and S-1, that is an oral fluoropyrimidine derivative consisting of 5-fluorouracil. Methods: Patients with advanced pancreatobiliary tract cancers were eligible for this clinical trial. The 12 patients, in whom a curative operation was not feasible, were enrolled in this study. Patients received S-1 orally at 80 mg/m2 total daily dose on days 1 to 28, followed by a 14 day recovery period. They also received VPA orally at 15 mg/m2 total daily dose, twice daily. Results: One patient had partial response (PR); ten patients were recorded as stable disease (SD); and one patient showed progressive disease (PD). Eight patients had clinically signif...