Scaling adult dose and schedule of anticancer agents to children.

PURPOSE: Objective of this work was to extend pharmacokinetic scaling theory of the writer for bolus dosing to include the case of constant-rate i.v. dosing over fixed interval so as to allow projection of adult dose and schedule of typically administered anticancer agents to children.
METHODS: The basis for the scaling is the requirement of time-scaled likeness of the plasma concentrations of an agent for adult and child. Algebraic expressions are established for describing the time history of the concentrations, and formulas for dose and dosing interval are determined so as to ensure the requirement on concentrations.
RESULTS: Scaling results for simple drug behavior are illustrated using clinical data for the anticancer agent carboplatin. Basic aspects of the theory are confirmed for dose and dosing interval of adult and 4-year-old child. The theory is also shown to describe tolerable doses for children when scaled from adult dosing requirements and to have application in determining dosing conditions for children requiring individualized dosing because of renal impairment. Scaling with more complex drug behavior is illustrated using preclinical and clinical data for the anticancer agent docetaxel. Adult-to-child scaling is demonstrated and shown to be consistent with previously reported clinical data. Additional consideration is given to the anticancer agents etoposide and melphalan, as widely used in pediatric chemotherapy, and also to the modern practice of combination chemotherapy.
CONCLUSIONS: Basic theory for scaling adult dose and schedule of anticancer agents to children is presented and demonstrated to be plausible in providing insight into existing and proposed pediatric treatment protocols.