Pharmacokinetics of chemotherapeutic agents in children’s oncology

Rationale: Little is known about the PK of the various classes of chemotherapy in children. Insight in the PK of the various classes of chemotherapy in children and, especially, in infants may result in improved dosing guidelines and/or individualized dosing regimens based on therapeutic drug monitoring, ultimately resulting in better clinical outcome. The aim is that future dosing of children with cancer will be evidence-based, as a result of the population PK data that will be generated with this project. As the projects covers several different chemotherapeutic drugs, the results will be highly relevant, as it will optimize the regimen in total, instead of only studying one single drug.

Objective: To assess the pharmacokinetics of various cytotoxic agents (carboplatin, cisplatin, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, methotrexate and vincristine) and their known metabolites (if applicable) in children to characterize the age-related changes in pharmacokinetics.

Study design: Prospective observational study

Study population: Patients aged 0-17 years treated in the PMC who will receive intravenously administered carboplatin, cisplatin, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, methotrexate or vincristine, that all have a present central line to sample blood for pharmacokinetics.

Main study parameters/endpoints: Pharmacokinetic parameters (i.e. clearance and volume of distribution) will be assessed using non-linear mixed effects modelling (NONMEM). Influence of relevant co-variates will be assessed by standard model building methods.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The patient has no direct benefit from participating in this study. The data obtained in this study will be used to assess the population PK of various classes of chemotherapeutic agents in children and infants with cancer. The only consequence of study participation is that additional blood samples (maximum of 8 samples of 1 ml once or twice) will be withdrawn. The here applied sampling strategy is minimally invasive, since all the patients that are included already have a central line. The volume of blood that is withdrawn for the study does not exceed the recommended maximum. Sampling, using a flexible time scheme, will only be requested during regular hospital visits.

Thus, insight in the PK of the various classes of chemotherapy in children and, especially, in infants may result in improved dosing guidelines and/or individualized dosing regimens based on therapeutic drug monitoring, ultimately resulting in better clinical outcome. The aim is that future dosing of children with cancer will be evidence-based, as a result of the population PK data that will be generated with this project. As the projects covers several different chemotherapeutic drugs, the results will be highly relevant, as it will optimize the regimen in total, instead of only studying one single drug.

START of the study: 01-02-2019
END of the study: 01-02-2022