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

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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; Forestier, Erik; Heyman, Mats; Uges, Donald R. A.; de Graaf, Siebold S. N.

I: British Journal of Haematology, Vol. 142, Nr. 4, 2008, s. 616-621.

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Lonnerholm, G, Frost, B-M, Abrahamsson, J, Behrendtz, M, Castor, A, Forestier, E, Heyman, M, Uges, DRA & de Graaf, SSN 2008, 'Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia', British Journal of Haematology, vol. 142, nr. 4, s. 616-621. https://doi.org/10.1111/j.1365-2141.2008.07235.x

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Lonnerholm, Gudmar ; Frost, Britt-Marie ; Abrahamsson, Jonas ; Behrendtz, Mikael ; Castor, Anders ; Forestier, Erik ; Heyman, Mats ; Uges, Donald R. A. ; de Graaf, Siebold S. N. / Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia. I: British Journal of Haematology. 2008 ; Vol. 142, Nr. 4. s. 616-621.

RIS

TY - JOUR

T1 - Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia

AU - Lonnerholm, Gudmar

AU - Frost, Britt-Marie

AU - Abrahamsson, Jonas

AU - Behrendtz, Mikael

AU - Castor, Anders

AU - Forestier, Erik

AU - Heyman, Mats

AU - Uges, Donald R. A.

AU - de Graaf, Siebold S. N.

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - pharmacokinetics

KW - drug effect

KW - vincristine

KW - acute lymphoblastic leukemia

KW - childhood

U2 - 10.1111/j.1365-2141.2008.07235.x

DO - 10.1111/j.1365-2141.2008.07235.x

M3 - Article

VL - 142

SP - 616

EP - 621

JO - British Journal of Haematology

T2 - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 4

ER -