Pharmacokinetic studies in children with cancer.
We reviewed the current status of our knowledge of pharmacokinetics and pharmacodynamics of some anti-neoplastic drugs, used in the treatment of childhood cancer. Extrapolation of data from pharmacokinetic studies in adults to the paediatric population is often not feasible. Specific studies in children are needed. Of all reviewed anti-neoplastic drugs methotrexate appears to be most extensively studied. Methotrexate pharmacokinetics is correlated with toxicity and response to therapy, and it has been shown that individualized adaptive dosing of methotrexate is correlated with a better response to therapy without increasing toxicity in children with ALL and osteosarcoma. Of most of the other reviewed anti-neoplastic drugs it is demonstrated that pharmacokinetics is correlated with toxicity, and of some drugs a relationship of pharmacokinetics with response to therapy is demonstrated as well. In case of cytarabine, etoposide, and teniposide, individualized dosing also appears to be feasible. However, there is no evidence that this strategy improves response to therapy. Specifically data on pharmacokinetic and pharmacodynamic correlations and effect of pharmacokinetically guided, individualized dosing are important for the design of optimal cancer chemotherapy for individual patients. Unfortunately for a considerable number of anti-neoplastic drugs these specific data are lacking in children and future research is needed.
Groninger
E
E
Department of Paediatric Oncology Haematology, Beatrix Children's Hospital, Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. ellisgroninger@home.nl
Proost
J H
JH
de Graaf
S S N
SS
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D013810:Therapeutic Equivalency
D000970:Antineoplastic Agents