Trial Information

Pharmacokinetics of Actinomycin D in Children With Cancer

OBJECTIVES:

- Determine the pharmacokinetics (PKs) of dactinomycin in pediatric patients with cancer.

- Determine the degree of interpatient variation in the PKs of this drug.

- Determine the influence of characteristics such as age, tumor type, and concurrent
therapy on drug PKs in these patients.

- Correlate drug PKs with clinical response and toxicity observed in these patients,
focusing particularly on the incidence of severe liver toxicity or veno-occlusive
disease.

- Correlate pharmacogenetic variability with clinical and PK data.

OUTLINE: This is a multicenter study.

Patients undergo blood collection for pharmacokinetic sampling of dactinomycin at baseline
(prior to the initiation of dactinomycin) and periodically during course 1 of chemotherapy.
An additional blood sample is obtained before or after treatment for the collection of
peripheral blood lymphocytes. DNA from these cells is isolated and investigated for genetic
variation in genes relevant to the pharmacology of dactinomycin. Plasma concentrations of
dactinomycin are determined by liquid chromatography mass spectrometry analysis.

Patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.