Potential impact of dose-banding for anticancer therapy in paediatrics based on pharmacokinetics

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.