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PURPOSE The purpose of our study was to investigate the pharmacology of clofarabine and its triphosphate and the pharmacodynamic actions in circulating blasts obtained from acute leukemia patients who entered a Phase I clinical trial of clofarabine. EXPERIMENTAL DESIGN Adults with refractory acute leukemias including lymphoblastic (ALL), myelogenous (AML)(More)
Tumor growth profiles were simulated for 2 years using the Wang and Claret models under a phase 3 clinical trial design. Profiles were censored when tumor size increased >20% from nadir similar to clinical practice. The percent of patients censored varied from 0% (perfect case) to 100% (real-life case). The model used to generate the data was then fit to(More)
Clinical trial simulation is the application of old technologies, e.g., Monte Carlo simulation, to a new problem, that problem being how to maximize the information content obtained during the drug development process with an intent to have the greatest chance of "success" in a clinical trial. When the information content of the drug is high, then(More)
There are many reasons for wishing to determine the rate of uptake of a drug from blood into brain parenchyma. However, when faced with doing so for the first time, choosing a method can be a formidable task. There are at least 7 methods from which to choose: indicator dilution, brain uptake index, microdialysis, external registration, PET scanning, in situ(More)
PURPOSE The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic(More)
PURPOSE To determine the safety, tolerability, and pharmacokinetics and to seek preliminary evidence of anticancer activity of tasidotin (ILX651), a novel dolastatin analogue, when administered as a 30-minute i.v. infusion weekly for 3 weeks every 4 weeks. EXPERIMENTAL DESIGN Thirty patients with advanced solid malignancies were treated with 82 courses at(More)
PURPOSE To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of tasidotin (ILX651), a dolastatin-15 analogue, when administered on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors. PATIENTS AND METHODS Thirty-two patients were treated with 92 courses of tasidotin through seven dose levels(More)
PURPOSE To introduce partially linear mixed effects models (PLMEMs), to illustrate their use, and to compare the power and Type I error rate in detecting a covariate effect with nonlinear mixed effects modeling using NONMEM. METHODS Sparse concentration-time data from males and females (1:1) were simulated under a 1-compartment oral model where clearance(More)
PURPOSE To determine the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of the dolastatin-15 analogue, tasidotin (ILX651), when administered i.v. daily for 5 days every 3 weeks. EXPERIMENTAL DESIGN Thirty-six patients with advanced solid tumors received a total of 114 courses through eight dose levels ranging from 2.3 to 36.3(More)
Quality population modeling and simulation analyses and reports are something every modeler desires. However, little attention in the literature has been paid to what constitutes quality regarding population analyses. Very rarely do published manuscripts contain any statement about quality assurance of the modeling results contained therein. The purpose of(More)