BACKGROUND/AIM: Pancreatobiliary tract cancers are amongst the most aggressive human cancers. Histone deacetylase (HDAC) is well-known to be associated with tumorigenesis through epigenetic regulation and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We conducted a clinical trial of combination therapy using valproic acid (VPA, a HDACI) and S-1, which is an oral fluoropyrimidine derivative consisting of 5-fluorouracil. PATIENTS AND METHODS: Patients with advanced pancreatobiliary tract cancers were eligible for this clinical trial. Twelve patients, in whom a curative operation was not feasible, were enrolled in the study. Patients received S-1 orally at a daily dose of 80 mg/m(2) for 28 days, followed by a 14-day recovery period. They also received VPA orally at a total daily dose of 15 mg/kg, twice daily. RESULTS: One patient had partial response (PR); ten patients were recorded with stable disease (SD); and one patient showed progressive disease (PD). Eight patients had clinically significant drug-related adverse events. The most frequent adverse events were platelet depletion and fatigue. Grade 3/4 adverse events, including anemia and platelet depletion, were observed. Significant increases in blood concentrations of VPA were confirmed 2 and 4 weeks after VPA administration. CONCLUSION: Combination therapy of VPA and S-1 for patients with pancreatobiliary tract cancers had a manageable safety profile and preliminary antitumor activity. Copyright
BACKGROUND/AIM: Pancreatobiliary tract cancers are amongst the most aggressive humancancers. Histone deacetylase (HDAC) is well-known to be associated with tumorigenesis through epigenetic regulation and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We conducted a clinical trial of combination therapy using valproic acid (VPA, a HDACI) and S-1, which is an oral fluoropyrimidine derivative consisting of 5-fluorouracil. PATIENTS AND METHODS: Patients with advanced pancreatobiliary tract cancers were eligible for this clinical trial. Twelve patients, in whom a curative operation was not feasible, were enrolled in the study. Patients received S-1 orally at a daily dose of 80 mg/m(2) for 28 days, followed by a 14-day recovery period. They also received VPA orally at a total daily dose of 15 mg/kg, twice daily. RESULTS: One patient had partial response (PR); ten patients were recorded with stable disease (SD); and one patient showed progressive disease (PD). Eight patients had clinically significant drug-related adverse events. The most frequent adverse events were platelet depletion and fatigue. Grade 3/4 adverse events, including anemia and platelet depletion, were observed. Significant increases in blood concentrations of VPA were confirmed 2 and 4 weeks after VPA administration. CONCLUSION: Combination therapy of VPA and S-1 for patients with pancreatobiliary tract cancers had a manageable safety profile and preliminary antitumor activity. Copyright
Authors: Sumera Rizvi; Shahid A Khan; Christopher L Hallemeier; Robin K Kelley; Gregory J Gores Journal: Nat Rev Clin Oncol Date: 2017-10-10 Impact factor: 66.675
Authors: Jennifer Yang; Matthew R Farren; Daniel Ahn; Tanios Bekaii-Saab; Gregory B Lesinski Journal: Expert Opin Ther Targets Date: 2017-03-17 Impact factor: 6.902
Authors: Manuela Terranova-Barberio; Biagio Pecori; Maria Serena Roca; Serena Imbimbo; Francesca Bruzzese; Alessandra Leone; Paolo Muto; Paolo Delrio; Antonio Avallone; Alfredo Budillon; Elena Di Gennaro Journal: J Exp Clin Cancer Res Date: 2017-12-06