• Population PK parameters for dactinomycin and VCR
  
• Demographic and/or physiological factors that are determinants of dactinomycin and VCR disposition
  

• Pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic characteristics of dactinomycin and vincristine (VCR)
  
• Pharmacogenetic profiles of patients receiving dactinomycin and VCR
  
• Correlation between genetic variation in drug metabolizing enzymes and drug transporters and observed drug PKs and PDs in children
  
• Creation of population PK and PD models to assess the effect of drug exposure on toxicity and outcomes
  
• Correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes
  

OBJECTIVES:

Primary

• To characterize the pharmacokinetics (PKs) of dactinomycin in infants, children, and adolescents with cancer.
• To identify demographic or physiological factors that are determinants of dactinomycin disposition.
• To characterize the PKs of vincristine (VCR) in infants, children, and adolescents with cancer.
• To identify demographic or physiological factors that are determinants of VCR disposition.

Secondary

• To examine the correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes.
• To explore the PK, pharmacodynamic, and pharmacogenetic relationships of dactinomycin and VCR in children with cancer.

OUTLINE: This is a multicenter study.

Patients undergo blood and urine collection prior to, periodically during, and after treatment with dactinomycin and vincristine for pharmacokinetic, pharmacodynamic, and pharmacogenetic analysis. Samples are analyzed using a liquid chromatography-tandem mass spectrometry assay. Genomic DNA extracted from peripheral blood mononuclear cells is isolated and analyzed by polymerase chain reaction and genotyping assays for genetic variation in genes relevant to the pharmacology of dactinomycin and vincristine.

After the final pharmacokinetic sample is collected, patients are followed for up to 6 months.