Document Detail


Malnourished Malawian patients presenting with large Wilms tumours have a decreased vincristine clearance rate.
MedLine Citation:
PMID:  20382523     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: In developing countries, patients with a Wilms' tumour often present late with a high degree of malnutrition and large tumours. We investigated whether this affects vincristine pharmacokinetics. METHODS: Patients newly diagnosed with Wilms' tumour in Malawi and the UK were included. We documented anthropometric parameters, nutritional status and tumour size. Vincristine (1.50 mg/m(2)) was administered as part of the standard chemotherapy regimen. Vincristine plasma concentrations were measured at several time points by liquid chromatography-mass spectrometry. Vincristine pharmacokinetic parameters (clearance and area under the curve) were calculated by non-compartmental analysis. RESULTS: Eleven Malawian and 8 UK patients were included. Mean Z-score of (corrected) weight for height was significantly lower in the Malawian patients than in the UK patients (-2.3 versus 0.42, p<0.0001). Mean tumour weight at diagnosis was significantly larger in Malawian patients (2.8 kg versus 0.7 kg, p=0.007). Mean vincristine logClearance was lower in Malawian as compared to UK patients (2.2 versus 2.6 ml/min, p=0.001). Mean logAUC values were higher in Malawian than in UK patients (3.8 versus 3.5 microg/mlmin, p=0.003). This difference is reflected in the, on average, 1.98-fold larger vincristine AUC values for Malawian patients. The difference in AUC values was statistically significantly explained by nutritional status (p=0.043). CONCLUSION: Malnourished patients in Malawi exhibited lower vincristine clearance rates and thus higher AUC values than a comparable patient population with a better nutritional status in the UK. In malnourished patients, dose reductions may need to be considered to prevent an increased incidence and severity of toxicity.
Authors:
Trijn Israels; Carola W N Damen; Michael Cole; Nan van Geloven; Alan V Boddy; Huib N Caron; Jos H Beijnen; Elizabeth M Molyneux; Gareth J Veal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-09
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  46     ISSN:  1879-0852     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-16     Completed Date:  2010-10-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  1841-7     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Paediatrics, College of Medicine, University of Malawi, Blantyre, Malawi. t.israels@amc.uva.nl
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Antineoplastic Agents, Phytogenic / pharmacokinetics*
Area Under Curve
Child
Female
Humans
Kidney Neoplasms / complications,  drug therapy,  metabolism*
Malawi
Male
Malnutrition / complications*,  metabolism
Metabolic Clearance Rate
Vincristine / pharmacokinetics*
Wilms Tumor / complications,  drug therapy,  metabolism*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 57-22-7/Vincristine

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