Research Topics
Genomes and Genes | J H M SchellensSummaryAffiliation: The Netherlands Cancer Institute Country: The Netherlands Publications
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Publications
Phase I pharmacokinetic and pharmacodynamic study of the prenyl transferase inhibitor AZD3409 in patients with advanced cancerN M G M Appels
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, Amsterdam 1066 EC, The Netherlands
Br J Cancer 98:1951-8. 2008..This study supports the rationale to implement biological effect studies in clinical trials with biologically active anticancer drugs to define optimal dosing regimens...
Abrogation of the G2 checkpoint by inhibition of Wee-1 kinase results in sensitization of p53-deficient tumor cells to DNA-damaging agentsSuzanne Leijen
Department of Experimental Therapy, The Netherlands Caner Institute, Amsterdam, The Netherlands
Curr Clin Pharmacol 5:186-91. 2010..Preliminary results show good tolerability and promising anti-cancer activity...
Concise drug review: pazopanib and axitinibRobin M J M van Geel
Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Oncologist 17:1081-9. 2012....
Lapatinib for advanced or metastatic breast cancerFrans L Opdam
The Netherlands Cancer Institute, Department of Clinical Pharmacology, Postbus 90203, 1006 BE Amsterdam, The Netherlands
Oncologist 17:536-42. 2012..Results of ongoing randomized phase III studies with lapatinib or trastuzumab in combination with taxanes as first-line agents for metastatic breast cancer as well as in the neoadjuvant and adjuvant settings are awaited...
Long-term platinum retention after treatment with cisplatin and oxaliplatinElke E M Brouwers
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
BMC Clin Pharmacol 8:7. 2008..The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin...
Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patientsMarie Christine W Gast
Department of Pharmacy and Pharmacology, Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
BMC Cancer 8:389. 2008..We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival...
Part 1: background, methodology, and clinical adoption of pharmacogeneticsMaarten J Deenen
The Netherlands Cancer Institute, Department of Medical Oncology, Amsterdam, The Netherlands
Oncologist 16:811-9. 2011..Opportunities for patient-tailored pharmacotherapy are highlighted...
TrastuzumabAnnelies H Boekhout
Division of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Oncologist 16:800-10. 2011..Main toxicity is reduction in the left ventricular ejection fraction, which in a minority of patients can become symptomatic, but in many patients is at least partly reversible. Long-term safety needs to be further determined...
[Management recommendations in patients with methotrexate intoxication]J H M Schellens
Nederlands Kanker Instituut Antoni van Leeuwenhoek Ziekenhuis, afd Medische Oncologie, Plesmanlaan 121, 1066 CX Amsterdam
Ned Tijdschr Geneeskd 151:337-41. 2007....
Gene polymorphisms, pharmacokinetics, and hematological toxicity in advanced non-small-cell lung cancer patients receiving cisplatin/gemcitabineM Joerger
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Cancer Chemother Pharmacol 69:25-33. 2012..This study quantified the impact of drug pathway-associated genetic variants on the pharmacokinetics (PK) of gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer (NSCLC)...
A pharmacokinetic and safety study of a novel polymeric paclitaxel formulation for oral applicationS A Veltkamp
Division of Experimental Therapy, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Cancer Chemother Pharmacol 59:43-50. 2007..To investigate the pharmacokinetics, safety, and tolerability of a new oral formulation of paclitaxel containing the polymer polyvinyl acetate phthalate in patients with advanced solid tumors...
Novel paclitaxel formulations for oral application: a phase I pharmacokinetic study in patients with solid tumoursS A Veltkamp
Division of Experimental Therapy, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066, Amsterdam, The Netherlands
Cancer Chemother Pharmacol 60:635-42. 2007..Moreover, the tolerability and safety of the formulations was studied. In addition, single nucleotide polymorphisms in the multidrug resistance (MDR1) gene were determined...
Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancerH H Helgason
Department of Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, and Faculty of Pharmaceutical Sciences, Utrecht University, The Netherlands
Br J Cancer 95:794-800. 2006..5 months and overall survival was 16 months. The pharmacokinetics revealed moderate inter- and low intrapatient variability. Weekly oral paclitaxel, combined with CsA, is active in patients with advanced breast cancer...
Dose-finding and pharmacokinetic study of orally administered indibulin (D-24851) to patients with advanced solid tumorsR L Oostendorp
Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Invest New Drugs 28:163-70. 2010..Continued dose-escalation was unlikely to yield any increase in exposure of indibulin. The formulation needs optimization to increase the systemic exposure upon oral administration...
Pharmacokinetics of eribulin mesylate in patients with solid tumors and hepatic impairmentL A Devriese
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Cancer Chemother Pharmacol 70:823-32. 2012..The aim of this study was to determine the plasma pharmacokinetics of eribulin mesylate in patients with solid tumors with mild and moderate hepatic impairment...
Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapyM Joerger
Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Lung Cancer 74:310-7. 2011..The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy...
Phase I and pharmacokinetic study of the combination of topotecan and ifosfamide administered intravenously every 3 weeksT Kerbusch
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Br J Cancer 90:2268-77. 2004....
Weekly oral paclitaxel as first-line treatment in patients with advanced gastric cancerC M F Kruijtzer
The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Ann Oncol 14:197-204. 2003..h/ml in week 2. The intrapatient variability in the AUC was 12%. CONCLUSIONS: Oral paclitaxel in combination with CsA is both active and safe in chemonaïve patients with advanced gastric cancer. Toxicities were mainly gastrointestinal...
A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancerS A Veltkamp
Division of Experimental Therapy, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
Br J Cancer 95:729-34. 2006..Remarkably, the SMEOF#3 formulation resulted in a significantly lower T(max) than orally applied Taxol, probably due to the excipients in the SMEOF#3 formulation resulting in a higher absorption rate of paclitaxel...
Inductively coupled plasma mass spectrometric analysis of the total amount of platinum in DNA extracts from peripheral blood mononuclear cells and tissue from patients treated with cisplatinE E M Brouwers
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands
Anal Bioanal Chem 391:577-85. 2008..The advantages of the presented ICP-MS technique were demonstrated by the analysis of PBMCs, normal gastric tissue, and gastric tumour tissue of patients treated with cisplatin...
Phase I dose-finding and pharmacokinetic trial of orally administered indibulin (D-24851) to patients with solid tumorsI E L M Kuppens
Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066, CX Amsterdam, The Netherlands
Invest New Drugs 25:227-35. 2007..This study is continued, evaluating indibulin administered as capsules on the recommended dose level of 60 mg daily for 14 days...
Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumorF J P Hoebers
Department of Radiotherapy, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Cancer Chemother Pharmacol 61:1075-81. 2008..In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated...
PK/PD model of indisulam and capecitabine: interaction causes excessive myelosuppressionA S Zandvliet
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Clin Pharmacol Ther 83:829-39. 2008..The combination of 550 mg/m(2) indisulam and 1,250 mg/m(2) capecitabine twice daily was considered safe...
Trabectedin (Yondelis, formerly ET-743), a mass balance study in patients with advanced cancerJ H Beumer
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands
Invest New Drugs 23:429-36. 2005..4% (3-h administration schedule). The excretion of unchanged trabectedin is very low both in faeces and in urine (< 1% of dose). In conclusion, trabectedin is extensively metabolised and principally excreted in the faeces...
Phase I and pharmacological study of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777) in combination with gemcitabine and cisplatin in patients with advanced solid tumoursW S Siegel-Lakhai
The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Br J Cancer 93:1222-9. 2005..i.d. in combination with gemcitabine 1000 mg m(-2) and cisplatin 75 mg m(-2). This combination showed evidence of antitumour activity and warrants further evaluation in a phase II setting...
A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumoursW S Siegel-Lakhai
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Br J Cancer 98:1320-6. 2008..The higher incidence of toxicities observed during cycle 2 can be explained by a time-dependent pharmacokinetic drug-drug interaction...
Oral bioavailability of docetaxel in combination with OC144-093 (ONT-093)I E L M Kuppens
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Cancer Chemother Pharmacol 55:72-8. 2005..Furthermore, the safety of combined treatment was determined and whether known functional genetic polymorphisms of the MDR1 gene could be associated with variability in docetaxel pharmacokinetics was also investigated...
Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancerJ H M Schellens
The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
Br J Cancer 88:814-21. 2003..Randomised studies are needed to determine whether the adaptive dosing strategy results in better efficacy than standard dosing...
Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometryJ H Beumer
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Invest New Drugs 25:327-34. 2007..Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities...
Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancerM Crul
Netherlands Cancer Institute and Academic Medical Centre, Amsterdam, The Netherlands
J Clin Oncol 20:2726-35. 2002..To determine the maximum-tolerated dose, toxicities, and pharmacokinetics of R115777, a farnesyl transferase inhibitor, when administered continuously via the oral route...
Eribulin mesylate pharmacokinetics in patients with solid tumors receiving repeated oral ketoconazoleL A Devriese
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Invest New Drugs 31:381-9. 2013..3 %) achieved stable disease as best overall response. Conclusions The results indicate that eribulin mesylate can be safely co-administered with ketoconazole. Drug-drug interactions are not expected with other CYP3A4 inhibitors...
A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumoursD S Boss
Division of Medical Oncology, Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
Br J Cancer 106:1598-604. 2012....
Population pharmacokinetic-pharmacodynamic analysis of trastuzumab-associated cardiotoxicityJ G C van Hasselt
Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Clin Pharmacol Ther 90:126-32. 2011..9% increase in sensitivity (decrease in EC₅₀) at the maximum cumulative anthracycline dose. The developed population PK-PD model may be used to establish optimal treatment and cardiac monitoring strategies for trastuzumab...
Phase I and pharmacological study of daily oral administration of perifosine (D-21266) in patients with advanced solid tumoursM Crul
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Eur J Cancer 38:1615-21. 2002..Therefore, MTD was established at 200 mg/day. The pharmacokinetic studies suggested dose proportionality...
Phase II and pharmacologic study of weekly oral paclitaxel plus cyclosporine in patients with advanced non-small-cell lung cancerC M F Kruijtzer
Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
J Clin Oncol 20:4508-16. 2002..The intrapatient variability (%CV) of the AUC was 14.5%. CONCLUSION: Oral paclitaxel plus CsA is active and safe in advanced NSCLC, including in patients previously treated with chemotherapy...
Evaluation of α2-integrin expression as a biomarker for tumor growth inhibition for the investigational integrin inhibitor E7820 in preclinical and clinical studiesRon J Keizer
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
AAPS J 13:230-9. 2011..Moderate inhibition of α(2)-integrin expression corresponded to tumor stasis in mice, and similar levels could be reached in patients with the dose level of 100 mg qd...
Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumoursD S Boss
Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Ann Oncol 21:884-94. 2010..Three phase I studies assessed the clinical safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5438 when administered in different dosing schedules...
Improvement of oral drug treatment by temporary inhibition of drug transporters and/or cytochrome P450 in the gastrointestinal tract and liver: an overviewC M F Kruijtzer
Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Oncologist 7:516-30. 2002..Future randomized studies will, hopefully, confirm that this strategy for oral treatment is at least as equally effective and safe as standard intravenous administration of these drugs...
Development and validation of LC-MS/MS assays for the quantification of E7080 and metabolites in various human biological matricesA C Dubbelman
Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
J Chromatogr B Analyt Technol Biomed Life Sci 887:25-34. 2012..At the other concentrations the accuracies were within ±15% of the nominal concentration with CV values below 15%. The developed methods have successfully been applied in a mass balance study of E7080...
Quantitative analysis of docetaxel in human plasma using liquid chromatography coupled with tandem mass spectrometryI E L M Kuppens
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Biomed Chromatogr 19:355-61. 2005..25 ng/mL. The assay was applied successfully in several clinical and pharmacological studies with docetaxel...
Investigational study of tamoxifen phase I metabolites using chromatographic and spectroscopic analytical techniquesS F Teunissen
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands
J Pharm Biomed Anal 55:518-26. 2011..In total, 19 metabolites have been identified in these serum samples. Additionally a synthetic method for the preparation of the putative metabolite 3',4'-dihydroxytamoxifen is described...
Validation of high-performance liquid chromatography-tandem mass spectrometry assays for the quantification of eribulin (E7389) in various biological matricesA C Dubbelman
Department of Clinical Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands
J Chromatogr B Analyt Technol Biomed Life Sci 879:1149-55. 2011..5 and 5 months, respectively. In conclusion, the validation results show that the assays are specific and accurate and can therefore adequately be applied to support clinical studies of eribulin...
Determinants of the elimination of methotrexate and 7-hydroxy-methotrexate following high-dose infusional therapy to cancer patientsM Joerger
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, and Department of Biomedical Analysis, Faculty of Pharmaceutical Sciences, Utrecht University, The Netherlands
Br J Clin Pharmacol 62:71-80. 2006..To characterize determinants of the elimination of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) in patients receiving high-dose MTX therapy (HDMTX)...
Quantitative analysis of gemcitabine triphosphate in human peripheral blood mononuclear cells using weak anion-exchange liquid chromatography coupled with tandem mass spectrometryS A Veltkamp
Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
J Mass Spectrom 41:1633-42. 2006..18 ng/0.648 mg protein = 0.047 ng/10(6) cells or 94 fmol/10(6) cells). This highly sensitive assay is capable of quantifying about 200-fold lower concentrations of dFdCTP in human PBMCs than currently available methods...
Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918C M F Kruijtzer
Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
J Clin Oncol 20:2943-50. 2002..CONCLUSION: Coadministration of the BCRP and P-gp inhibitor GF120918 resulted in a significant increase of the systemic exposure of oral topotecan. The apparent oral bioavailability increased from 40.0% without to 97.1% with GF120918...
Safety and pharmacology of paclitaxel in patients with impaired liver function: a population pharmacokinetic-pharmacodynamic studyM Joerger
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Br J Clin Pharmacol 64:622-33. 2007..To assess quantitatively the safety and pharmacology of paclitaxel in patients with moderate to severe hepatic impairment...
Therapeutic drug monitoring of non-anticancer drugs in cancer patientsM Joerger
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Methods Find Exp Clin Pharmacol 26:531-45. 2004..In all cases, treating physicians have to consider the variability in patient age, disease stage, comedication, organ function and protein level to weigh the pros and cons of TDM in the individual cancer patient...
Yondelis (trabectedin, ET-743): the development of an anticancer agent of marine originCh van Kesteren
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
Anticancer Drugs 14:487-502. 2003..The present review describes the development of ET-743, highlighting chemical properties, mode of action, metabolism and preclinical and clinical studies...
Development and validation of a quantitative assay for the determination of tamoxifen and its five main phase I metabolites in human serum using liquid chromatography coupled with tandem mass spectrometryS F Teunissen
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
J Chromatogr B Analyt Technol Biomed Life Sci 879:1677-85. 2011..The applicability of the assay was demonstrated and it is now successfully used to support clinical studies in which patient-specific dose optimization is performed based on serum concentrations of tamoxifen metabolites...
A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancerN E Schoemaker
Antoni van Leeuwenhoek Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Br J Cancer 91:1434-41. 2004..Irinotecan is an effective and safe second-line treatment for colorectal cancer. The schedules examined yielded equivalent results, indicating that there is no advantage of the prolonged vs short infusion schedules...
Hepatotoxicity and metabolism of trabectedin: a literature reviewJ H Beumer
Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Pharmacol Res 51:391-8. 2005..Monitoring of plasma levels of liver enzymes ensures safe use of trabectedin in the clinic. Future investigations must be aimed at elucidating the mechanism of trabectedin hepatotoxicity...
Intravenous-to-oral switch in anticancer chemotherapy: a focus on docetaxel and paclitaxelS L W Koolen
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Clin Pharmacol Ther 87:126-9. 2010..Preclinical studies in Pgp-deficient and wild-type mice demonstrated that modulation of either Pgp or CYP3A resulted in high systemic exposure to docetaxel or paclitaxel. This concept could successfully be translated to clinical trials...
DNA-based drug interactions of cisplatinM Crul
The Netherlands Cancer Institute, Amsterdam, The Netherlands
Cancer Treat Rev 28:291-303. 2002..In this paper, we review the pre-clinical and clinical studies investigating the observed interactions between cisplatin, the antimetabolites, taxanes, and topoisomerase inhibitors on the DNA level...
Quantification of cabazitaxel, its metabolite docetaxel and the determination of the demethylated metabolites RPR112698 and RPR123142 as docetaxel equivalents in human plasma by liquid chromatography-tandem mass spectrometryA Kort
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands Electronic address
J Chromatogr B Analyt Technol Biomed Life Sci 925:117-23. 2013..In conclusion, this method can be applied to support clinical pharmacokinetic studies with the novel anticancer drug cabazitaxel...
Development and validation of LC-MS/MS assays for the quantification of bendamustine and its metabolites in human plasma and urineA C Dubbelman
Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
J Chromatogr B Analyt Technol Biomed Life Sci 893:92-100. 2012..These methods were successfully applied to evaluate the pharmacokinetic profile of bendamustine and its metabolites in cancer patients treated with bendamustine...
Circulating tumor cell detection in advanced non-small cell lung cancer patients by multi-marker QPCR analysisL A Devriese
Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Lung Cancer 75:242-7. 2012..CTCs may not only serve as a prognostic marker in selected tumor types, but may also be useful as pharmacodynamic marker in drug development...
A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancerT J Molloy
Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Br J Cancer 104:1913-9. 2011..The detection of circulating tumour cells (CTCs) has been linked with poor prognosis in advanced breast cancer. Relatively few studies have been undertaken to study the clinical relevance of CTCs in early-stage breast cancer...
A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecinN E Schoemaker
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Br J Cancer 87:608-14. 2002..Haematological toxicity was relatively mild, but serious bladder toxicity was encountered which is typical for camptothecin and was found dose limiting...
[The concomitant use of radiotherapy and chemotherapy for the treatment of solid malignant tumors]H Bartelink
afd. Radiotherapie, Het Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis, Plesmanlaan 121, 1066 CX Amsterdam
Ned Tijdschr Geneeskd 146:504-8. 2002..Major further improvement can be expected from the design and use of new drugs that influence the pathways leading to cell death after irradiation...
Determination of oxaliplatin in human plasma and plasma ultrafiltrate by graphite-furnace atomic-absorption spectrometryE E M Brouwers
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands
Anal Bioanal Chem 382:1484-90. 2005..The validated ranges of quantification were 0.10-400 micromol L(-1) for human pUF and 0.50-400 micromol L(-1) for plasma. The assay is now successfully used to support pharmacokinetic studies of cancer patients treated with oxaliplatin...
Modulation of oral drug bioavailability: from preclinical mechanism to therapeutic applicationIsa E L M Kuppens
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Cancer Invest 23:443-64. 2005..Both are good examples of improvement of oral drug bioavailability by temporary inhibition of drug transporters in the gut epithelium...
Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a Dutch populationT M Bosch
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Mol Diagn Ther 10:175-85. 2006....
Interactions of serum albumin, valproic acid and carbamazepine with the pharmacokinetics of phenytoin in cancer patientsMarkus Joerger
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Basic Clin Pharmacol Toxicol 99:133-40. 2006..Significant alterations of the free fraction of phenytoin and free phenytoin by co-administration of valproic acid or carbamazepine suggest therapeutic drug monitoring of free phenytoin to be of potential benefit in cancer patients...
Method development and validation for the quantification of dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma by liquid chromatography coupled with tandem mass spectrometryN A G Lankheet
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, Amsterdam, The Netherlands
Biomed Chromatogr 27:466-76. 2013..1%) and precision (10.0%) for all analytes. This method was successfully applied for routine therapeutic drug monitoring purposes in patients treated with the investigated TKIs. Copyright © 2012 John Wiley & Sons, Ltd...
Importance of highly selective LC-MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifenN G L Jager
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Breast Cancer Res Treat 133:793-8. 2012..We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples...
Carcinogen and anticancer drug transport by Mrp2 in vivo: studies using Mrp2 (Abcc2) knockout miceM L H Vlaming
Division of Experimental Therapy, The Netherlands Cancer Institute, Division of Experimental Therapy, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
J Pharmacol Exp Ther 318:319-27. 2006..Our results demonstrate that the Mrp2-/- mouse provides a valuable tool for studies of the impact of Mrp2 on behavior of drugs and other toxins, especially when combined with other ABC transporter knockout mice...
SELDI-TOF MS serum protein profiles in breast cancer: assessment of robustness and validityM C W Gast
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
Cancer Biomark 2:235-48. 2006..This finding stresses that, when reporting on a potential biomarker, confirmation of both robustness and validity is essential in obtaining its true clinical applicability...
Phase I evaluation of telatinib, a VEGF receptor tyrosine kinase inhibitor, in combination with bevacizumab in subjects with advanced solid tumorsM H G Langenberg
Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
Ann Oncol 22:2508-15. 2011..This phase I study investigated telatinib, an oral tyrosine kinase inhibitor targeting VEGFR-2, combined with bevacizumab, in adults with solid tumors...
Pharmacokinetic-pharmacodynamic guided trial design in oncologyCh van Kesteren
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervnaart Hospital, Amsterdam, The Netherlands
Invest New Drugs 21:225-41. 2003..The application of PK-PD modeling in each separate stage of (pre)clinical drug development of anticancer agents is discussed. The implementation of this approach is illustrated with the clinical development of docetaxel...
Ciprofloxacin strongly inhibits clozapine metabolism: two case reportsE E M Brouwers
Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Clin Drug Investig 29:59-63. 2009..This might cause severe adverse effects. We advise using another antibacterial agent or reducing the clozapine dose and monitoring clozapine levels when this antipsychotic agent is used in combination with ciprofloxacin...
Monitoring of platinum surface contamination in seven Dutch hospital pharmacies using inductively coupled plasma mass spectrometryE E M Brouwers
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, and Department of Clinical Pharmacology and Pharmacy, Free University Medical Centre, Amsterdam, The Netherlands
Int Arch Occup Environ Health 80:689-99. 2007..To develop, validate, and apply a method for the determination of platinum contamination, originating from cisplatinum, oxaliplatinum, and carboplatinum...
The combined use of radiotherapy and chemotherapy in the treatment of solid tumoursH Bartelink
Department of Radiotherapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Eur J Cancer 38:216-22. 2002..Examples include topoisomerase 1 (topo1) inhibitors, alkyl-lysophospholipids, epidermal growth factor receptor (EGFR) receptor inhibitors...
Evaluation of the bioequivalence of tablets and capsules containing the novel anticancer agent R115777 (Zarnestra) in patients with advanced solid tumorsM Crul
The Netherlands Cancer Institute, Department of Medical Oncology, Amsterdam
Eur J Drug Metab Pharmacokinet 27:61-5. 2002..81-1.09 and 0.83-1.03, which is within the critical range for bioequivalence of 0.80-1.25. In conclusion, the established pharmacokinetic parameters demonstrate that the capsule and tablet formulations of R115777 are interchangeable...
Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor lurtotecan in phase II studiesJ H M Schellens
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam
Invest New Drugs 20:83-93. 2002..Prospective implementation of large scale population pharmacokinetic-dynamic analysis is feasible and important to establish whether interpatient variability in drug exposure is a major determinant of toxicity or activity...
Bioanalytical methods for determination of tamoxifen and its phase I metabolites: a reviewS F Teunissen
Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Anal Chim Acta 683:21-37. 2010..This review can be used as a resource for method transfer and development of analytical methods used to support pharmacokinetic and pharmacodynamic studies of tamoxifen and its phase I metabolites...
In vitro pharmacokinetic study of the novel anticancer agent E7070: red blood cell and plasma protein binding in human bloodH J G D van den Bongard
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
Anticancer Drugs 14:405-10. 2003..In conclusion, E7070 in whole blood is preferentially bound to RBC and exhibits high plasma protein binding. The non-linear distribution of E7070 in humans can be caused, in part at least, by saturable binding of E7070 to RBC...
Propofol extravasation in a breast cancer patientE J M Huijbers
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Louwesweg 6, Amsterdam, The Netherlands
J Oncol Pharm Pract 14:195-8. 2008..Propofol extravasation did not result in tissue necrosis in this case. AC chemotherapy could be administered safely 3 days after propofol extravasation...
The Dutch vision of clinical pharmacologyJ H M Schellens
Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Clin Pharmacol Ther 85:366-8. 2009..The Dutch Society for Clinical Pharmacology and Biopharmacy offers answers to these questions and presents a new model for clinical pharmacology...
Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trialAnnelies H Boekhout
The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Division of Clinical Pharmacology, Amsterdam, The Netherlands
J Clin Oncol 29:3862-8. 2011..Additional analyses of the hot flash score over the full 12 weeks of treatment were performed...
Part 3: Pharmacogenetic variability in phase II anticancer drug metabolismMaarten J Deenen
The Netherlands Cancer Institute, Department of Medical Oncology, Amsterdam, The Netherlands
Oncologist 16:992-1005. 2011..Based on the literature reviewed, opportunities for patient-tailored anticancer therapy are proposed...
Part 4: pharmacogenetic variability in anticancer pharmacodynamic drug effectsMaarten J Deenen
Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Oncologist 16:1006-20. 2011..Potential implications and opportunities for patient and drug selection for genotype-driven anticancer therapy are outlined...
Part 2: pharmacogenetic variability in drug transport and phase I anticancer drug metabolismMaarten J Deenen
Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Oncologist 16:820-34. 2011..Based on the literature reviewed, opportunities for patient-tailored anticancer therapy are presented...
A population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modellingH J G D van den Bongard
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Cancer Chemother Pharmacol 50:16-24. 2002..The purpose of this study was to develop a population pharmacokinetic model for Cremophor EL used as a formulation vehicle for paclitaxel...
Quantitative analysis of the novel depsipeptide anticancer drug Kahalalide F in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray ionization tandem mass spectrometryE Stokvis
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
J Mass Spectrom 37:992-1000. 2002..91% or better at these concentrations. The analyte was stable in plasma under all relevant conditions evaluated and for a period of 16 h after reconstituting plasma extracts for LC analysis at ambient temperature...
Phase I and pharmacokinetic study of E7070, a novel chloroindolyl sulfonamide cell-cycle inhibitor, administered as a one-hour infusion every three weeks in patients with advanced cancerE Raymond
Department of Medicine, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
J Clin Oncol 20:3508-21. 2002..The objectives were to determine the maximum-tolerated dose, the recommended dose, the dose-limiting toxicity, the pharmacokinetics, and the activity of E7070, a novel cell-cycle inhibitor...
Development and validation of limited sampling strategies for prediction of the systemic exposure to the novel anticancer agent E7070 (N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide)Charlotte Van Kesteren
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Br J Clin Pharmacol 54:463-71. 2002..The aim of this study was to develop and validate limited sampling strategies for the prediction of E7070 exposure in two different treatment schedules for phase II studies using the Bayesian estimation approach...
No topoisomerase I alteration in a neuroblastoma model with in vivo acquired resistance to irinotecanL Calvet
Pharmacology and New Treatments in Cancer (UPRES EA 3535, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
Br J Cancer 91:1205-12. 2004..Our results suggest a novel resistance mechanism, probably not involving the mechanisms usually observed in vitro...
Phase I clinical and pharmacokinetic study of E7070, a novel sulfonamide given as a 5-day continuous infusion repeated every 3 weeks in patients with solid tumours. A study by the EORTC Early Clinical Study Group (ECSG)C Terret
Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France
Eur J Cancer 39:1097-104. 2003..The risk of myelosuppression became significant with an AUC greater than 4000 microg h/ml. The recommended dose of E7070 for further studies is 96 mg/m(2)/day when administered on a 5-day continuous infusion schedule every 3 weeks...
Pharmacokinetics of low-dose doxorubicin and metabolites in patients with AIDS-related Kaposi sarcomaM Joerger
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Cancer Chemother Pharmacol 55:488-96. 2005....
Phase II study of XR 5000, an inhibitor of topoisomerases I and II, in advanced colorectal cancerF Caponigro
EORTC Early Clinical Studies Group, New Drug Development Program, Brussels, Belgium
Eur J Cancer 38:70-4. 2002..Despite the good toxicity profile, these results do not support further trials with XR 5000 in metastatic colorectal cancer...
The role of nuclear receptors in pharmacokinetic drug-drug interactions in oncologyS Harmsen
Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Biomedical Analysis, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
Cancer Treat Rev 33:369-80. 2007....
Population pharmacokinetics of the novel anticancer agent E7070 during four phase I studies: model building and validationCh van Kesteren
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam
J Clin Oncol 20:4065-73. 2002..A population pharmacokinetic model was designed and validated to describe the pharmacokinetics of E7070 at all four treatment schedules and to identify the possible influences of patient characteristics on the pharmacokinetic parameters...
Future opportunities in preventing cisplatin induced ototoxicityJ H van den Berg
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, P O Box 90440, 1006 BK Amsterdam, The Netherlands
Cancer Treat Rev 32:390-7. 2006..Positive results of an otoprotector in clinical practice may increase the effectiveness of cisplatin therapy and can improve the quality of life for a large group of patients...
Isolated hepatic perfusion for the treatment of colorectal metastases confined to the liver: recent trends and perspectivesJ Rothbarth
Department of Surgery, K6-R, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Eur J Cancer 40:1812-24. 2004..The results of these studies show that high response rates and high survival rates can be achieved by IHP. In this article, the current status, recent developments and future perspectives of IHP are discussed...
Quantitative analysis of ES-285, an investigational marine anticancer drug, in human, mouse, rat, and dog plasma using coupled liquid chromatography and tandem mass spectrometryE Stokvis
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
J Mass Spectrom 38:548-54. 2003..ES-285 was stable during all steps of the assay. Thus far this method has been used successfully to analyze over 500 samples in pre-clinical trials, and will be implemented in the planned clinical phase I studies...
Switching from an analogous to a stable isotopically labeled internal standard for the LC-MS/MS quantitation of the novel anticancer drug Kahalalide F significantly improves assay performanceE Stokvis
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Biomed Chromatogr 18:400-2. 2004..Similar results can be expected for other LC-MS/MS assays. Therefore, we emphasize the need for an SIL internal standard for accurate and precise LC-MS/MS assays of drugs in biological matrices...
Quantitative analysis of the novel anticancer drug ABT-518, a matrix metalloproteinase inhibitor, plus the screening of six metabolites in human plasma using high-performance liquid chromatography coupled with electrospray tandem mass spectrometryE Stokvis
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
J Mass Spectrom 39:277-88. 2004..We believe that the method described in this paper using an alkaline mobile phase in combination with a basic stable analytical column may also be generally useful for the bioanalysis of other basic drugs...
Determination of total platinum in plasma and plasma ultrafiltrate, from subjects dosed with the platinum-containing N-(2-hydroxypropyl)methacrylamide copolymer AP5280, by use of graphite-furnace Zeeman atomic-absorption spectrometryM M Tibben
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Anal Bioanal Chem 373:233-6. 2002..Analysis of free platinum in PUF was performed by use of a previously validated and reported assay from our institute in which the same instrumental method is used...
Phase II trial with S-1 in chemotherapy-naïve patients with gastric cancer. A trial performed by the EORTC Early Clinical Studies Group (ECSG)P Chollet
Department of Medical Oncology, Centre Jean Perrin, 58 rue Montalembert, F 63011, Cedex 1, Clermont Ferrand, France
Eur J Cancer 39:1264-70. 2003....
EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancerJ Van den Brande
Department of Medical Oncology, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium
Br J Cancer 88:648-53. 2003..The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations...
Sensitive inductively coupled plasma mass spectrometry assay for the determination of platinum originating from cisplatin, carboplatin, and oxaliplatin in human plasma ultrafiltrateE E M Brouwers
Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, and Department of Biomedical Analysis, Faculty of Pharmaceutical Sciences, Utrecht University, The Netherlands
J Mass Spectrom 41:1186-94. 2006..50 ng l-1 to 1.00x10(5) ng l-1 in plasma ultrafiltrate for all three platinum compounds. The assay is now successfully used to support pharmacokinetic studies in cancer patients treated with cisplatin, carboplatin, or oxaliplatin...
