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Population pharmaco...
Population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients : a study by the EORTC-PAMM-NDDG
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Joerger, Markus (author)
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Huitema, Alwin D R (author)
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Richel, Dick J (author)
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Dittrich, Christian (author)
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Pavlidis, Nikolas (author)
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Briasoulis, Evangelos (author)
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Vermorken, Jan B (author)
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Strocchi, Elena (author)
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Martoni, Andrea (author)
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Sorio, Roberto (author)
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Sleeboom, Henk P (author)
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Izquierdo, Miguel A (author)
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Jodrell, Duncan I (author)
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Féty, Régine (author)
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de Bruijn, Ernst (author)
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Hempel, Georg (author)
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- Karlsson, Mats (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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Tranchand, Brigitte (author)
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Schrijvers, Ad H G J (author)
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Twelves, Chris (author)
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Beijnen, Jos H (author)
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Schellens, Jan H M (author)
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: Clinical Pharmacokinetics. - 0312-5963 .- 1179-1926. ; 46:12, s. 1051-1068
- Related links:
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https://urn.kb.se/re...
Abstract
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- Aims: 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 mu mol . h/L [95% CI 889, 1001] vs 602 mu mol . 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
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Breast cancer
- Cyclophosphamide
- Doxorubicin
- Pharmacokinetic modelling
- Population pharmacokinetics
- PHARMACY
- FARMACI
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Joerger, Markus
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Huitema, Alwin D ...
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Richel, Dick J
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Dittrich, Christ ...
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Pavlidis, Nikola ...
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Briasoulis, Evan ...
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show more...
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Vermorken, Jan B
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Strocchi, Elena
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Martoni, Andrea
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Sorio, Roberto
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Sleeboom, Henk P
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Izquierdo, Migue ...
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Jodrell, Duncan ...
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Féty, Régine
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de Bruijn, Ernst
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Hempel, Georg
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Karlsson, Mats
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Tranchand, Brigi ...
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Schrijvers, Ad H ...
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Twelves, Chris
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Beijnen, Jos H
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Schellens, Jan H ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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Clinical Pharmac ...
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Uppsala University