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
Φόρτωση...
Ημερομηνία
Συγγραφείς
Joerger, M.
Huitema, A. D.
Richel, D. J.
Dittrich, C.
Pavlidis, N.
Briasoulis, E.
Vermorken, J. B.
Strocchi, E.
Martoni, A.
Sorio, R.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Clin Cancer Res
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
PURPOSE: 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.
Περιγραφή
Λέξεις-κλειδιά
Antineoplastic Agents/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Area Under Curve, Carboplatin/*pharmacokinetics/*pharmacology, Disease Progression, Drug Design, Europe, Female, Humans, Kinetics, Neutropenia, Ovarian Neoplasms/*drug therapy/*genetics/*pathology, Paclitaxel/*pharmacokinetics/*pharmacology, Predictive Value of Tests, Thrombocytopenia, Treatment Outcome
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/17975154
http://clincancerres.aacrjournals.org/content/13/21/6410.full.pdf
http://clincancerres.aacrjournals.org/content/13/21/6410.full.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής