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Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia

Lonnerholm, Gudmar; Frost, Britt-Marie; Abrahamsson, Jonas; Behrendtz, Mikael; Castor, Anders LU ; Forestier, Erik; Heyman, Mats; Uges, Donald R. A. and de Graaf, Siebold S. N. (2008) In British Journal of Haematology 142(4). p.616-621
Abstract
Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We here report clinical data (median follow-up time 10.5 years, range 7.3-12 years) for 86 children with B-cell precursor ALL, in whom vincristine kinetics were studied on treatment day 1. The median total plasma clearance was 429 and 331 ml/min per m(2) and the area under the plasma concentration-time curve (AUC) was 4.49 and 5.40 mg/l x min in relapse and non-relapse patients, respectively (not significant). In standard risk patients, where... (More)
Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We here report clinical data (median follow-up time 10.5 years, range 7.3-12 years) for 86 children with B-cell precursor ALL, in whom vincristine kinetics were studied on treatment day 1. The median total plasma clearance was 429 and 331 ml/min per m(2) and the area under the plasma concentration-time curve (AUC) was 4.49 and 5.40 mg/l x min in relapse and non-relapse patients, respectively (not significant). In standard risk patients, where treatment depends more heavily on vincristine than in other subgroups, the relative risk (RR) of relapse was significantly increased for patients with clearance values above median (RR 5.2; P = 0.036), or AUC values below median (RR 5.8; P = 0.025). Our data suggest a relationship between the antileukemic effect and the systemic exposure of the drug, which warrants further studies. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pharmacokinetics, drug effect, vincristine, acute lymphoblastic leukemia, childhood
in
British Journal of Haematology
volume
142
issue
4
pages
616 - 621
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000257796800012
  • scopus:47649125266
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2008.07235.x
language
English
LU publication?
yes
id
a04c6c00-b68f-44c2-8b28-d2f6222afddc (old id 1253926)
date added to LUP
2008-11-04 09:53:25
date last changed
2017-05-21 03:34:44
@article{a04c6c00-b68f-44c2-8b28-d2f6222afddc,
  abstract     = {Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We here report clinical data (median follow-up time 10.5 years, range 7.3-12 years) for 86 children with B-cell precursor ALL, in whom vincristine kinetics were studied on treatment day 1. The median total plasma clearance was 429 and 331 ml/min per m(2) and the area under the plasma concentration-time curve (AUC) was 4.49 and 5.40 mg/l x min in relapse and non-relapse patients, respectively (not significant). In standard risk patients, where treatment depends more heavily on vincristine than in other subgroups, the relative risk (RR) of relapse was significantly increased for patients with clearance values above median (RR 5.2; P = 0.036), or AUC values below median (RR 5.8; P = 0.025). Our data suggest a relationship between the antileukemic effect and the systemic exposure of the drug, which warrants further studies.},
  author       = {Lonnerholm, Gudmar and Frost, Britt-Marie and Abrahamsson, Jonas and Behrendtz, Mikael and Castor, Anders and Forestier, Erik and Heyman, Mats and Uges, Donald R. A. and de Graaf, Siebold S. N.},
  issn         = {0007-1048},
  keyword      = {pharmacokinetics,drug effect,vincristine,acute lymphoblastic leukemia,childhood},
  language     = {eng},
  number       = {4},
  pages        = {616--621},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia},
  url          = {http://dx.doi.org/10.1111/j.1365-2141.2008.07235.x},
  volume       = {142},
  year         = {2008},
}