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- Palle, Josefine, et al.
(författare)
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Doxorubicin pharmacokinetics is correlated to the effect of induction therapy in children with acute myeloid leukemia
- 2006
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Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 17:4, s. 385-392
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Tidskriftsartikel (refereegranskat)abstract
- We studied the pharmacokinetics of doxorubicin in 41 children treated for newly diagnosed acute myeloid leukemia. Doxorubicin, 75 mg/m(2) body surface area, was administered by constant i.v. infusion over 8 h. Four children with Down's syndrome (DS), 1.2-2.3 years old, had a median total body clearance of 523 ml/min/m(2). The median clearance in non-DS children, 0.6-1.8 years old (n=4) and 2.5-17.7 years old (n=33), was 446 and 538 ml/min/m(2), respectively. Patients who went into complete remission (CR) after induction therapy had a significantly higher median plasma concentration of doxorubicin than those who did not, 249 compared with 180 ng/ml, respectively (P=0.036; analysis restricted to non-DS patients). Doxorubicin plasma concentration was an independent factor for CR, both in univariate (P=0.031) and multivariate analysis including sex, age and white blood cell count at diagnosis (P=0.021). Patients who reached CR had a significantly lower doxorubicin clearance than those who did not, 513 and 657 ml/min/m(2), respectively (P=0.017). In conclusion, doxorubicin plasma concentration and total body clearance during up-front treatment were correlated to the effect of induction therapy. Prospective studies should be performed to confirm the concentration-effect relationship and explore the possibility of therapeutic monitoring.
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| 2. |
- Palle, Josefine, et al.
(författare)
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Etoposide pharmacokinetics in children treated for acute myeloid leukemia
- 2006
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Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 17:9, s. 1087-1094
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Tidskriftsartikel (refereegranskat)abstract
- We studied the pharmacokinetics of etoposide in 45 children treated for newly diagnosed acute myeloid leukemia. Etopcoside, 100 mg/m(2) body surface area/24h, was administered by 96-h continuous intravenous infusion. Concomitantly, the children received cytarabine 200 mg/m(2)/24 h by intravenous infusion and 6-thioguanine 100 mg/m(2) twice daily orally. Median total body clearance in children 0.5-11.8 (n=4) and 2.3-17.7 years old (n=36) without Down's syndrome was 17.1 and 17.6 ml/min/m(2), respectively (P=0.96). Five children with Down's syndrome had a median clearance of 13.6 ml/min/m(2) (P=0.067 compared with non-Down's syndrome children). Eighteen of the children received a second identical treatment course 3-4 weeks later; there was a significant correlation between individual clearance values (p=0.56; P=0.017). We found no significant correlation between etoposide pharmacolkinetics and the remission rate or the relapse rate. In conclusion, our findings indicate that special dose-calculation guidelines for infants above 3 months old are not substantiated by age-dependent pharmacolkinetics of etoposide. Down's syndrome children might be candidates for dose reduction if our data are confirmed in larger numbers of patients. Low course-to-course variability indicates that pharmacolkinetically guided dosing of etoposide might be clinically relevant, if larger studies can demonstrate that this approach decreases toxicity or increases response rates.
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