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Barnett S, Hellmann F, Parke E, et al. Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients. Eur J Cancer. 2021;doi: 10.1016/j.ejca.2021.09.014.
Barnett, S., Hellmann, F., Parke, E., Makin, G., Tweddle, D. A., Osborne, C., Hempel, G., & Veal, G. J. (2021). Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients. European journal of cancer (Oxford, England : 1990), . https://doi.org/10.1016/j.ejca.2021.09.014
Barnett, Shelby, et al. "Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients." European journal of cancer (Oxford, England : 1990) vol. (2021). doi: https://doi.org/10.1016/j.ejca.2021.09.014
Barnett S, Hellmann F, Parke E, Makin G, Tweddle DA, Osborne C, Hempel G, Veal GJ. Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients. Eur J Cancer. 2021 Oct 14; doi: 10.1016/j.ejca.2021.09.014. Epub 2021 Oct 14. PMID: 34657763.
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Eur J Cancer. 2021 Oct 14; doi: 10.1016/j.ejca.2021.09.014. Epub 2021 Oct 14.

Vincristine dosing, drug exposure and therapeutic drug monitoring in neonate and infant cancer patients.

European journal of cancer (Oxford, England : 1990)

Shelby Barnett, Farina Hellmann, Elizabeth Parke, Guy Makin, Deborah A Tweddle, Caroline Osborne, Georg Hempel, Gareth J Veal

Affiliations

  1. Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
  2. Department of Pharmaceutical and Medical Chemistry, University of Münster, Münster, Germany.
  3. Division of Cancer Sciences, University of Manchester, Manchester, UK; Royal Manchester Children's Hospital, Manchester, UK.
  4. Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK; Great North Children's Hospital, Newcastle, UK.
  5. Pharmacy Department, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
  6. Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK. Electronic address: [email protected].

PMID: 34657763 DOI: 10.1016/j.ejca.2021.09.014

Abstract

BACKGROUND: The anticancer drug vincristine is associated with potentially dose-limiting side-effects, including neurotoxicity and myelosuppression. However, there currently exists a lack of published clinical pharmacology data relating to its use in neonate and infant patients. We report a study investigating vincristine dosing and drug exposure, alongside the feasibility and impact of a therapeutic drug monitoring treatment approach, in this challenging patient population.

PATIENTS AND METHODS: Vincristine pharmacokinetic data from a total of 57 childhood cancer patients, including 26 neonates and infants, were used to characterise a population pharmacokinetic model. Vincristine was administered at doses of 0.02-0.05 mg/kg or 0.75-1.5 mg/m

RESULTS: A two-compartment model provided the best fit for the population analysis. There was no significant difference in vincristine clearance normalised for body surface area between neonates/infants and older children. Lower doses administered to neonates and infants resulted in significantly lower drug exposures (area under the curve [AUC]), compared with older children (p = 0.047). Vincristine doses of <0.05 mg/kg in neonates and infants resulted in significantly lower AUC values than observed in those receiving doses of ≥0.05 mg/kg (p ≤ 0.0001). Therapeutic drug monitoring was shown to be feasible, effective and well tolerated in neonates and infants experiencing suboptimal drug exposures.

CONCLUSION: Doses of <0.05 mg/kg should not be used in neonate and infant patients because of a high risk of patients experiencing potentially suboptimal drug exposures. Therapeutic drug monitoring approaches in neonates and infants are supported by the data generated, with a proposed target therapeutic window of 50-100 μg/l∗h.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keywords: Chemotherapy; Dosing; Infants; Neonates; Paediatrics; Pharmacokinetics; Therapeutic drug monitoring; Vincristine

Conflict of interest statement

Conflict of interest statement The authors have no financial relationships relevant to the work contained in this article to disclose and no other conflicts of interest to disclose.

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