Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group

Απλή σελίδα τεκμηρίου
dc.contributor.authorJoerger, M.en
dc.contributor.authorHuitema, A. D.en
dc.contributor.authorRichel, D. J.en
dc.contributor.authorDittrich, C.en
dc.contributor.authorPavlidis, N.en
dc.contributor.authorBriasoulis, E.en
dc.contributor.authorVermorken, J. B.en
dc.contributor.authorStrocchi, E.en
dc.contributor.authorMartoni, A.en
dc.contributor.authorSorio, R.en
dc.contributor.authorSleeboom, H. P.en
dc.contributor.authorIzquierdo, M. A.en
dc.contributor.authorJodrell, D. I.en
dc.contributor.authorCalvert, H.en
dc.contributor.authorBoddy, A. V.en
dc.contributor.authorHollema, H.en
dc.contributor.authorFety, R.en
dc.contributor.authorVan der Vijgh, W. J.en
dc.contributor.authorHempel, G.en
dc.contributor.authorChatelut, E.en
dc.contributor.authorKarlsson, M.en
dc.contributor.authorWilkins, J.en
dc.contributor.authorTranchand, B.en
dc.contributor.authorSchrijvers, A. H.en
dc.contributor.authorTwelves, C.en
dc.contributor.authorBeijnen, J. H.en
dc.contributor.authorSchellens, J. H.en
dc.date.accessioned2015-11-24T18:57:53Z
dc.date.available2015-11-24T18:57:53Z
dc.identifier.issn1078-0432-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19219
dc.rightsDefault Licence-
dc.subjectAntineoplastic Agents/therapeutic useen
dc.subjectAntineoplastic Combined Chemotherapy Protocols/therapeutic useen
dc.subjectArea Under Curveen
dc.subjectCarboplatin/*pharmacokinetics/*pharmacologyen
dc.subjectDisease Progressionen
dc.subjectDrug Designen
dc.subjectEuropeen
dc.subjectFemaleen
dc.subjectHumansen
dc.subjectKineticsen
dc.subjectNeutropeniaen
dc.subjectOvarian Neoplasms/*drug therapy/*genetics/*pathologyen
dc.subjectPaclitaxel/*pharmacokinetics/*pharmacologyen
dc.subjectPredictive Value of Testsen
dc.subjectThrombocytopeniaen
dc.subjectTreatment Outcomeen
dc.titlePopulation pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development groupen
heal.abstractPURPOSE: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 micromol/L (t(C > 0.05-0.2)) predicts neutropenia. The objective of this study was to build a population pharmacokinetic-pharmacodynamic model of paclitaxel/carboplatin in ovarian cancer patients. EXPERIMENTAL DESIGN: One hundred thirty-nine ovarian cancer patients received paclitaxel (175 mg/m(2)) over 3 h followed by carboplatin area under the concentration-time curve 5 mg/mL*min over 30 min. Plasma concentration-time data were measured, and data were processed using nonlinear mixed-effect modeling. Semiphysiologic models with linear or sigmoidal maximum response and threshold models were adapted to the data. RESULTS: One hundred five patients had complete pharmacokinetic and toxicity data. In 34 patients with measurable disease, objective response rate was 76%. Neutrophil and thrombocyte counts were adequately described by an inhibitory linear response model. Paclitaxel t(C > 0.05) was significantly higher in patients with a complete (91.8 h) or partial (76.3 h) response compared with patients with progressive disease (31.5 h; P = 0.02 and 0.05, respectively). Patients with paclitaxel t(C > 0.05) > 61.4 h (mean value) had a longer time to disease progression compared with patients with paclitaxel t(C > 0.05) < 61.4 h (89.0 versus 61.9 weeks; P = 0.05). Paclitaxel t(C > 0.05) was a good predictor for severe neutropenia (P = 0.01), whereas carboplatin exposure (C(max) and area under the concentration-time curve) was the best predictor for thrombocytopenia (P < 10(-4)). CONCLUSIONS: In this group of patients, paclitaxel t(C > 0.05) is a good predictive marker for severe neutropenia and clinical outcome, whereas carboplatin exposure is a good predictive marker for thrombocytopenia.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1158/1078-0432.CCR-07-0064-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/17975154-
heal.identifier.secondaryhttp://clincancerres.aacrjournals.org/content/13/21/6410.full.pdf-
heal.journalNameClin Cancer Resen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2007-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

Αρχεία

Φάκελος/Πακέτο αδειών

Προβολή: 1 - 1 of 1
Μικρογραφία εικόνας
Ονομα:
license.txt
Μέγεθος:
1.74 KB
Μορφότυπο:
Item-specific license agreed upon to submission
Περιγραφή:
Κατεβάστε

Συλλογές

Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά) - ΙΑΤ