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

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.