Alwin D. R. Huitema

J. G. Coen van Hasselt3
Anthe S. Zandvliet3
Learn More
Pharmacokinetic-pharmacodynamic modeling using non-linear mixed effects modeling (NONMEM) is a powerful yet challenging technique, as the software is generally accessed from the command line. A graphical user interface, Piraña, was developed that offers a complete modeling environment for NONMEM, enabling both novice and advanced users to increase(More)
BACKGROUND The phase I program of anticancer agents usually consists of multiple dose escalation studies to select a safe dose for various administration schedules. We hypothesized that pharmacokinetic and pharmacodynamic (PK-PD) modeling of an initial phase I study (stage 1) can be used for selection of an optimal starting dose for subsequent studies(More)
The antiestrogenic drug tamoxifen is widely used in the treatment of estrogen receptor-α-positive breast cancer and substantially decreases recurrence and mortality rates. However, high interindividual variability in response is observed, calling for a personalized approach to tamoxifen treatment. Tamoxifen is bioactivated by cytochrome P450 (CYP) enzymes(More)
Hand–foot syndrome (HFS) is a side effect of sunitinib with considerable impact on quality of life. Seasonal variation and hyperhydrosis are possibly correlated to occurrence of HFS. Therefore, we proposed to study the prevalence of HFS in different seasons retrospectively and to study the relationship between sunitinib sweat secretion and HFS(More)
In population pharmacokinetic analyses, missing categorical data are often encountered. We evaluated several methods of performing covariate analyses with partially missing categorical covariate data. Missing data methods consisted of discarding data (DROP), additional effect parameter for the group with missing data (EXTRA), and mixture methods in which(More)
INTRODUCTION Modeling and simulation of pharmacokinetics and pharmacodynamics has previously been shown to be potentially useful in designing Phase I programs of novel anti-cancer agents that show hematological toxicity. In this analysis, a two-stage model-based trial design was evaluated retrospectively using data from the Phase I program with the aurora(More)
Trastuzumab treatment is associated with occurrence of cardiac toxicity, for which monitoring of the left ventricular ejection fraction (LVEF) is indicated. The performance of the currently used monitoring protocol as defined in the summary of product characteristics (SPC) is however unknown. The objective of this analysis was to develop a model-based(More)
In cancer chemotherapy neutropenia is a common dose-limiting toxicity. An ability to predict the neutropenic effects of cytotoxic agents based on proposed trial designs and models conditioned on previous studies would be valuable. The aim of this study was to evaluate the ability of a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for(More)
Hypertension and proteinuria are commonly observed side-effects for anti-angiogenic drugs targeting the VEGF pathway. In most cases, hypertension can be controlled by prescription of anti-hypertensive (AH) therapy, while proteinuria often requires dose reductions or dose delays. We aimed to construct a pharmacokinetic-pharmacodynamic (PK-PD) model for(More)
Background Omacetaxine mepesuccinate is indicated in adults with chronic myeloid leukemia resistant and/or intolerant to ≥ 2 tyrosine kinase inhibitor treatments. This phase I study assessed the disposition, elimination, and safety of (14)C-omacetaxine in patients with solid tumors. Methods The study comprised a 7-days pharmacokinetic assessment followed by(More)