BACKGROUND Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcin...

INTRODUCTION The phase III MPACT trial in patients with metastatic pancreatic cancer (MPC) demonstrated superior efficacy of nab-paclitaxel (nab-P) plus gemcitabine (Gem) compared with Gem monotherapy, including the primary endpoint of overall survival (OS; median 8.7 vs. 6.6 months; hazard ratio [HR] 0.72; P < 0.001). A significant treatment difference favoring nab-P + Gem over Gem was observe...

A serious pharmacokinetic interaction between cerivastatin (CER) and gemfibrozil (GEM) has been reported. In the present study, we examined the inhibitory effects of GEM and its metabolites, M3 and gemfibrozil 1-O-beta-glucuronide (GEM-1-O-glu), on the uptake of CER by human organic anion transporting polypeptide 2 (OATP2)-expressing cells and its metabolism in cytochrome P450 expression system...

PURPOSE There is no optimal dosing schedule of gemcitabine (GEM) and cisplatin (CDDP) combination for cancer patients with renal failure (RF) on hemodialysis (HD). The purpose of this study was to share our experience of using GEM and CDDP in such patients. METHODS The starting dose of GEM was defined based on single-agent treatment of two cancer patients with RF. Between November 2006 and Ju...

PURPOSE Investigate the efficacy and pharmacodynamic effects of MK-1775, a potent Wee1 inhibitor, in both monotherapy and in combination with gemcitabine (GEM) using a panel of p53-deficient and p53 wild-type human pancreatic cancer xenografts. EXPERIMENTAL DESIGN Nine individual patient-derived pancreatic cancer xenografts (6 with p53-deficient and 3 with p53 wild-type status) from the PancX...

Lack of effective therapy is a major problem in the treatment of pancreatic cancer. In the present study, we investigated a natural product, the extract of Pao Pereira (Pao), for its anti-pancreatic cancer effect in vitro and in vivo, either alone or in combination with the first-line chemotherapeutic drug gemcitabine (Gem). Pao induced dose-dependent apoptosis to all five tested pancreatic can...

BACKGROUND Gemcitabine (GEM) is widely used as an anticancer agent in several types of solid tumors. Silver nanoparticles (AgNPs) possess unique cytotoxic features and can induce apoptosis in a variety of cancer cells. In this study, we investigated whether the combination of GEM and AgNPs can exert synergistic cytotoxic effects in the human ovarian cancer cell line A2780. METHODS We synthesi...

BACKGROUND In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacy versus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emission tomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial. PATIENTS AND METHODS Patients with ...

PURPOSE Preclinical data shows improvements in response for the combination of imatinib mesylate (IM, Gleevec) and gemcitabine (GEM) therapy compared with GEM alone. Our goals were to determine the maximum tolerated dose of GEM and IM in combination, the pharmacokinetics of GEM in the absence and in the presence of IM, and IM pharmacokinetics in this combination. PATIENTS AND METHODS Patients...

Histone deacetylase (HDAC) is strongly associated with epigenetic regulation and carcinogenesis, and its inhibitors induce the differentiation or apoptosis of cancer cells. Valproic acid (VPA) is one of the clinically available HDAC inhibitors. We investigated the anticancer effects of VPA in combination with gemcitabine (GEM) in the human cholangiocarcinoma cell line HuCCT1, and explored the m...