Abstract 605: Investigating the potential impact of dose-banding for systemic anticancer therapy (SACT) in the pediatric setting based on pharmacokinetic evidence

Abstract

Abstract Background: In order to make systemic anticancer therapy (SACT) preparation more practicable, dose-banding approaches are currently being introduced in many clinical centers. This involves the individual dose for a particular patient being calculated according to a single body surface area (BSA) value per band, usually the mid-point of the band in which the actual BSA of the patient lies. Advantages of such an approach include a rationalization of chemotherapy provision, with the preparation of drugs with sufficient long-term stability feasible well in advance of treatment, reduced potential for medication errors and improved capacity planning of pharmacy production. The current study aimed to determine the potential impact of utilizing recently developed National Health Service in England (NHSE) dose-banding tables in a pediatric setting, according to pharmacokinetic criteria determined from previously-published clinical trials for a range of commonly used anticancer drugs. Methods: Using pharmacokinetic parameters obtained from 385 drug administrations in 352 children aged from 1 month to 18 years, treated with 5 drugs (dactinomycin, busulfan, carboplatin, cyclophosphamide, etoposide), individual exposures (area under the curve; AUC) obtained using doses rounded according to the published NHSE tables (or banded using the same method) were calculated and compared to those obtained by standard dose calculation methods. The patients included in the study were treated for a wide range of tumors including neuroblastoma, B cell non-Hodgkin's lymphoma, Wilms tumor, rhabdomyosarcoma and Ewing's sarcoma. Results: For all five drugs, the relative variation between the NHSE dose and the recommended dose (standard individually calculated dose) was between -6% and +5% as expected. Indeed, more marked differences were observed between the actual dose administered and the recommended dose for these retrospective datasets, particularly for carboplatin and dactinomycin. In terms of AUC, there was no statistically significant difference in precision between exposures obtained by the recommended dose and those obtained with dose-banding (absolute value of relative difference 15-34%). Conclusion: Based on pharmacokinetic data from 352 children, the results generated from the current study support the implementation of NHSE dose-banding tables, at least for the five drugs investigated here. Indeed, inter-patient variability in drug clearance and exposure would appear to far outweigh the impact of relatively small drug dose changes associated with dose-banding. Further evaluation of the effect of using dose-banding for other drugs would be needed to confirm these results and extend them to additional anticancer drugs. Citation Format: Melanie White-Koning, Caroline Osborne, Angelo Paci, Alan V. Boddy, Etienne Chatelut, Gareth J. Veal. Investigating the potential impact of dose-banding for systemic anticancer therapy (SACT) in the pediatric setting based on pharmacokinetic evidence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 605.