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Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

Janine R Hutson1, Sheila Weitzman, Tal Schechter

  • 1University of Toronto, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Ave, Toronto ON, M5G 1X8, Canada.

Expert Opinion on Drug Metabolism & Toxicology
|April 19, 2012
PubMed

Insights

Chemotherapy dosing in infants lacks high-quality data, often relying on empiric methods. This review highlights pharmacokinetic and pharmacogenetic factors to improve infant cancer treatment efficacy and safety.

Area of Science:

  • Pediatric Oncology
  • Pharmacology
  • Genetics

Background:

  • Optimal chemotherapy dosage regimens for infants are not well-established.
  • Current infant chemotherapy dosing is often extrapolated from older children, risking toxicity and treatment failure.
  • Balancing efficacy and toxicity is crucial for adherence and successful treatment in infants.

Purpose of the Study:

  • To review pharmacokinetic and pharmacogenetic considerations for chemotherapy in infants.
  • To provide practical recommendations for dosing adjustments of common chemotherapeutic agents in infants.

Main Methods:

  • Literature review of pharmacokinetic and pharmacogenetic data in pediatric oncology.
  • Analysis of existing chemotherapy dosing guidelines for infants.
  • Synthesis of evidence-based recommendations for infant chemotherapy administration.

Main Results:

  • Significant knowledge gaps exist in infant chemotherapy dosing.
  • Pharmacokinetic and pharmacogenetic factors significantly influence drug response and toxicity in infants.
  • Emerging evidence-based guidelines offer improvements over purely empiric dosing.

Conclusions:

  • Infant chemotherapy treatment has not kept pace with adult cancer advancements.
  • Further basic and clinical research is essential to understand age-dependent pharmacokinetic differences.
  • While progress has been made, chemotherapy dosing in neonates and infants remains largely empiric.
Abstract

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