Population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients: a study by the EORTC-PAMM-NDDG

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.authorFety, R.en
dc.contributor.authorde Bruijn, E.en
dc.contributor.authorHempel, G.en
dc.contributor.authorKarlsson, M.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.issn0312-5963-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19220
dc.rightsDefault Licence-
dc.subjectAlgorithmsen
dc.subjectAntibiotics, Antineoplastic/adverse effects/pharmacokinetics/therapeutic useen
dc.subjectAntineoplastic Agents, Alkylating/adverse effects/pharmacokinetics/therapeuticen
dc.subjectuseen
dc.subjectArea Under Curveen
dc.subjectBreast Neoplasms/*drug therapyen
dc.subjectCyclophosphamide/adverse effects/*pharmacokinetics/therapeutic useen
dc.subjectDoxorubicin/adverse effects/*pharmacokinetics/therapeutic useen
dc.subjectFemaleen
dc.subjectHematologic Diseases/chemically induceden
dc.subjectHumansen
dc.subjectMiddle Ageden
dc.subjectModels, Biologicalen
dc.subjectTreatment Outcomeen
dc.titlePopulation pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients: a study by the EORTC-PAMM-NDDGen
heal.abstractAIMS: To investigate the population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients. PATIENTS AND METHODS: Sixty-five female patients with early or advanced breast cancer received doxorubicin 60 mg/m(2) over 15 minutes followed by cyclophosphamide 600 mg/m(2) over 15 minutes. The plasma concentration-time data of both drugs were measured, and the relationship between drug pharmacokinetics and neutrophil counts was evaluated using nonlinear mixed-effect modelling. Relationships were explored between drug exposure (the area under the plasma concentration-time curve [AUC]), toxicity and tumour response. RESULTS: Fifty-nine patients had complete pharmacokinetic and toxicity data. In 50 patients with measurable disease, the objective response rate was 60%, with complete responses in 6% of patients. Both doxorubicin and cyclophosphamide pharmacokinetics were associated with neutrophil toxicity. Cyclophosphamide exposure (the AUC) was significantly higher in patients with at least stable disease (n = 44) than in patients with progressive disease (n = 6; 945 micromol . h/L [95% CI 889, 1001] vs 602 micromol . h/L [95% CI 379, 825], p = 0.0002). No such correlation was found for doxorubicin. Body surface area was positively correlated with doxorubicin clearance; AST and patient age were negatively correlated with doxorubicin clearance; creatinine clearance was positively correlated with doxorubicinol clearance; and occasional concurrent use of carbamazepine was positively correlated with cyclophosphamide clearance. CONCLUSIONS: The proposed inhibitory population pharmacokinetic-pharmacodynamic model adequately described individual neutrophil counts after administration of doxorubicin and cyclophosphamide. In this patient population, exposure to cyclophosphamide, as assessed by the AUC, might have been a predictor of the treatment response, whereas exposure to doxorubicin was not. A prospective study should validate cyclophosphamide exposure as a predictive marker for the treatment response and clinical outcome in this patient group.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/18027989-
heal.journalNameClin Pharmacokineten
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