Investigating the potential impact of dose banding for systemic anti-cancer therapy in the paediatric setting based on pharmacokinetic evidence

Eur J Cancer. 2018 Mar:91:56-67. doi: 10.1016/j.ejca.2017.11.029. Epub 2018 Jan 12.

Abstract

Background: To make systemic anti-cancer therapy (SACT) preparation more practicable, dose-banding approaches are currently being introduced in many clinical centres. The present study aimed to determine the potential impact of using recently developed National Health Service in England (NHSE) dose-banding tables in a paediatric setting.

Methods: Using pharmacokinetic parameters obtained from 385 drug administrations in 352 children aged from 1 month to 18 years, treated with five drugs (dactinomycin, busulfan, carboplatin, cyclophosphamide and etoposide), individual exposures (area under the plasma drug concentration versus time curve; AUC) obtained using doses rounded according to the published NHSE tables were calculated and compared with those obtained by standard dose calculation methods.

Results: For all five drugs, the relative variation between the NHSE dose and the recommended dose (RecDose) (standard individually calculated dose) was between -6% and +5% as expected. In terms of AUC, there was no statistically significant difference in precision between exposures obtained by the RecDose and those obtained with dose banding (absolute value of relative difference 15-34%).

Conclusion: Based on pharmacokinetic data for these five drugs, the results generated support the implementation of NHSE dose-banding tables. Indeed, inter-patient variability in drug clearance and exposure far outweighs the impact of relatively small drug dose changes associated with dose banding.

Keywords: Dose banding; Dosing regimen; Oncology; Paediatrics; Pharmacokinetics.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Busulfan / administration & dosage
  • Busulfan / pharmacokinetics
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacokinetics
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacokinetics
  • Dactinomycin / administration & dosage
  • Dactinomycin / pharmacokinetics
  • Drug Dosage Calculations*
  • Drug Monitoring
  • Etoposide / administration & dosage
  • Etoposide / pharmacokinetics
  • Humans
  • Infant
  • Models, Biological*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Patient Safety
  • Risk Factors

Substances

  • Antineoplastic Agents
  • Dactinomycin
  • Etoposide
  • Cyclophosphamide
  • Carboplatin
  • Busulfan