Evaluating the Side Effects and How Well Anticancer Drugs Work in Very Young Patients With Cancer

• Pharmacokinetic parameters [ Designated as safety issue: No ]
  
• Pharmacokinetic modelling comparing pharmacokinetic parameters to investigate the key factors involved in determining individual exposures to parent drugs and metabolites [ Designated as safety issue: No ]
  
• Influence of pharmacokinetic parameters and genotype for metabolizing enzyme on event-free survival [ Designated as safety issue: No ]
  
• Influence of pharmacokinetic parameters and genotype for metabolizing enzyme on toxicity [ Designated as safety issue: No ]
  

OBJECTIVES:

• Investigate inter-individual variability in the pharmacokinetics of selected anticancer drugs in infants and children age < 2 years on current dosing schedules.
• Compare drug exposures and degree of pharmacokinetic variability in children < 2 years with data obtained from published studies in older children.
• Relate inter-individual variability in pharmacokinetics and drug exposure to clinical toxicity and response.
• Use pharmacokinetic data in conjunction with clinical information obtained following treatment to investigate the suitability of current dosing regimens in infants and young children.

OUTLINE: This is a multicenter study. Patients are stratified according to age in months (0 to 6 vs 6 to 12 vs 12 to 24).

Patients receive carboplatin, cyclophosphamide, or etoposide according to the dosing regimen detailed in the clinical protocol on which the child is being treated.

Blood samples are collected from patients receiving 1 of the 3 drugs by central venous catheter periodically during treatment to measure pharmacokinetics of the specific drug. Additional blood samples are collected for DNA extraction and polymorphism analysis in CYP2B6, CYP2C9, and other metabolizing enzymes in addition to the determination of the genetic variation in multiple drug resistance.