A5000270744- Chronic Myeloid Leukemia Treatments
- Gastrointestinal Tumor Research and Treatment
- Renal cell carcinoma treatment
- Chronic Lymphocytic Leukemia Research
- Gastric Cancer Management and Outcomes
- Cancer Genomics and Diagnostics
- Platelet Disorders and Treatments
- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Drug Transport and Resistance Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Liver Disease Diagnosis and Treatment
- Neuroendocrine Tumor Research Advances
- Peptidase Inhibition and Analysis
- Gastrointestinal disorders and treatments
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- Multiple Myeloma Research and Treatments
- Renal and related cancers
- Sarcoma Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Metal complexes synthesis and properties
- Bone health and treatments
- Lanthanide and Transition Metal Complexes
Erasmus MC Cancer Institute
2011-2022
Gelre Hospitals
2022
Erasmus MC
2009-2018
St. Jude Children's Research Hospital
2010-2013
University Medical Center Groningen
2009-2012
Uppsala University
2012
Karolinska Institutet
2012
The Netherlands Cancer Institute
2009-2010
Leiden University Medical Center
2009-2010
Erasmus University Rotterdam
2010
To identify genetic markers in the pharmacokinetic and pharmacodynamic pathways of sunitinib that predispose for development toxicities: thrombocytopenia, leukopenia, mucosal inflammation, hand-foot syndrome, any toxicity according to National Cancer Institute Common Toxicity Criteria higher than grade 2.A multicenter pharmacogenetic association study was performed 219 patients treated with single-agent sunitinib. A total 31 single nucleotide polymorphisms 12 candidate genes, together...
Abstract Purpose: The objective of this study was to identify genetic polymorphisms related the pharmacokinetics and pharmacodynamics sunitinib that are associated with a prolonged progression-free survival (PFS) and/or overall (OS) in patients clear-cell metastatic renal cell cancer (mRCC) treated sunitinib. Experimental design: A retrospective multicenter pharmacogenetic association performed 136 mRCC total 30 11 candidate genes, together clinical characteristics were tested univariately...
Imatinib minimal (trough) plasma concentrations after one month of treatment have shown a significant association with clinical benefit in patients gastrointestinal stromal tumors (GIST). Considering that retrospective pharmacokinetic analysis has also suggested imatinib clearance increases over time soft tissue sarcoma and GIST, the primary aim this study was to assess systemic exposure at multiple points long-term prospective population study. As is mainly metabolized liver, our secondary...
Anticancer treatment with the tyrosine kinase inhibitor sunitinib causes thyroid dysfunction.Our objective was to investigate time course and underlying mechanisms of sunitinib-induced dysfunction.Thyroid function tests 83 patients on were collected retrospectively for their total duration between January 2006 November 2009 prospectively in 15 10 wk. Additionally, histology assessed rats (8 d; n = 10) after withdrawal (11 7) compared controls (n 7).Patients seen at a university outpatient...
Hypertension is an important side effect of sunitinib treatment. In a retrospective study in 255 patients, single-nucleotide polymorphisms (SNPs) vascular endothelial growth factor A (VEGFA), receptor (VEGFR)-2, endothelin-1 (ET-1), and endothelium-derived nitric oxide synthase (eNOS) were multivariately tested against hypertension grades changes systolic blood pressure (SBP), diastolic BP (DBP), mean arterial (MAP). Next, the association between survival patients with metastatic renal cell...
The bioavailability of orally administered imatinib is >90%, although the drug monocationic under acidic conditions in duodenum. In vitro, we found that transported by intestinal uptake carrier organic anion transporting polypeptide (OATP1A2) and this process sensitive to pH, rosuvastatin, genetic variants. However, a study patients with cancer, absorption was not associated OATP1A2 variants unaffected rosuvastatin. These findings highlight importance verifying clinical setting...
Assessment of tumor size changes is crucial in clinical trials and patient care. We compared imatinib-induced volume liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST Choi criteria their association with overall survival (OS).LM 84 GIST patients (training validation set) were evaluated using manual semi-automated Computed Tomography measurements at baseline, after 3, 6 12 months imatinib. The ability uni-dimensional (1D) three-dimensional (3D) detect...
For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable decrease over time, for which several mechanisms have In this study, we investigated if in alpha-1 acid glycoprotein (AGP) is the main cause of lowering time.We prospectively measured trough concentration (C min) values 28 patients with gastrointestinal stromal tumours, at 1, 3 12 months after start treatment. At same time points, AGP levels were...
Prior studies have demonstrated an organic anion transporter 6 (OAT6)-mediated accumulation of sorafenib in keratinocytes. The OAT6 inhibitor probenecid decreases uptake skin and might, therefore, decrease sorafenib-induced cutaneous adverse events. Here, the influence on pharmacokinetics toxicity was investigated. Pharmacokinetic sampling performed 16 patients steady-state treatment at days 1 15 study. Patients received (200-800 mg daily) combination with (500 two times daily (b.i.d.))...
5006 Background: To identify genetic markers in the pharmacokinetic and pharmacodynamic pathways of sunitinib that predispose for development toxicities; thrombocytopenia, leukopenia, mucosal inflammation, hand-foot syndrome ‘any toxicity according to Common Terminology Criteria > grade 2.’ Methods: A multicenter pharmacogenetic association study was performed 219 patients treated with single agent sunitinib. total 31 nucleotide polymorphisms 12 candidate genes, together several...
10014 Background: Imatinib is mainly metabolized in the liver. We therefore studied potential effects of metastatic liver involvement on exposure to imatinib patients with GIST. Additionally, as clearance from a retrospective analysis has been suggested decrease over time (Judson et al., Cancer Chemother Pharmacol, 2005), while 1 month steady state trough levels were be associated clinical benefit (Demetri J Clin Oncol, 2009), secondary endpoint our study was assess after multiple long-term...
Background: Assessment of tumor size changes is crucial in clinical trials and patient care.We compared imatinib-induced volume liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST Choi criteria their association with overall survival (OS).Methods: LM 84 GIST patients (training validation set) were evaluated using manual semi-automated Computed Tomography measurements at baseline, after 3, 6 12 months imatinib.The ability uni-dimensional (1D) three-dimensional (3D)...
Tamoxifen is a commonly prescribed drug in both early and metastatic breast cancer. Prospective studies Asian populations demonstrated that tamoxifen-related liver steatosis occurred more than 30% of the patients within 2 years after start treatment. No well-designed prospective on potential have been conducted Caucasian so far. Therefore, our study aimed to assess incidence for period population cancer treated with tamoxifen. Patients an indication adjuvant treatment tamoxifen were included...
10059 Background: Assessing antitumor effect of treatment is particularly important to guide changes and assess novel treatments in early clinical trials. We compared the sensitivity 3D 1D measurements detecting size liver metastases from GIST assessing response treatment. Methods: IM was given until progressive disease (PD) as assessed by RECIST. evaluated 58 patients (pts) manual (2 independent readers) semi-automated on CT-scans at baseline, after 6 12 months (mo) IM. Bland-Altman plots...
3098 Background: In patients treated with imatinib (Gleevec) a 4-fold interpatient variability in drug exposure exists, possibly as result of pharmacogenetic (PG) which implicates that some may be underdosed if fixed dose is used. this study we searched for genetic markers to predict the disposition imatinib, phenotypically expressed by ‘toxicity-adjusted-dose’ at 3 and 12 months treatment chronic myeloid leukemia gastrointestinal stromal tumor patients. Methods: A multicenter PG association...
4521 Background: The objective of this study was to identify genetic polymorphisms involved in the pharmacokinetics and pharmacodynamics sunitinib that are associated with progression-free survival (PFS) and/or overall (OS) patients metastatic renal cell cancer (mRCC). Methods: A multicenter pharmacogenetic association performed 136 clear-cell mRCC treated sunitinib. total 31 12 candidate genes, together clinical characteristics were tested univariately a Kaplan-Meier analysis for PFS as...