Doxorubicin pharmacokinetics is correlated to the effect of induction therapy in children with acute myeloid leukemia

Anticancer Drugs. 2006 Apr;17(4):385-92. doi: 10.1097/01.cad.0000198911.98442.16.


We studied the pharmacokinetics of doxorubicin in 41 children treated for newly diagnosed acute myeloid leukemia. Doxorubicin, 75 mg/m2 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/m2. 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/m2, 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/m2, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibiotics, Antineoplastic / pharmacokinetics*
  • Child
  • Child, Preschool
  • Down Syndrome / complications
  • Doxorubicin / analogs & derivatives
  • Doxorubicin / blood
  • Doxorubicin / pharmacokinetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute / blood
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male


  • Antibiotics, Antineoplastic
  • Doxorubicin
  • adriamycinol