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Therapeutic drug monitoring and dose adaptation of cisplatin in a newborn with hepatoblastoma: a case report

Lookup NU author(s): Professor Gareth Veal

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Abstract

© 2018 Springer-Verlag GmbH Germany, part of Springer Nature Purpose: Chemotherapy dosing in neonates represents a major clinical challenge because of a lack of clinical pharmacology information in this patient population. In this study, we investigate the use of cisplatin dose adaptation based on therapeutic drug monitoring in a 2-week-old neonate with localized hepatoblastoma. Methods: Cisplatin concentrations were determined in plasma and ultrafiltrate samples collected on each of six cycles of a monotherapy regimen, beginning with a dose of 1.6 mg/kg at 16 days of age. Pharmacokinetic data were analyzed to generate clearance (CL) and area under the curve (AUC0–∞) for each administration. Toxicity and clinical response were monitored. Results: The first cisplatin dose (1.6 mg/kg) resulted in an AUC0–∞ of 535 µg/mL · min, was well tolerated and associated with a good response. This AUC was, therefore, considered as an appropriate target for this patient. Increases in cisplatin CL were observed across consecutive treatment cycles, and, therefore, dose was gradually increased to finally reach 2.5 mg/kg on the sixth cycle. Treatment was well tolerated over the six courses and resulted in a good response, with the patient remaining in remission at 15 months. Cisplatin CL was significantly correlated to age (p = 0.013) and weight (p = 0.013). Conclusions: Our study provides useful data on the pharmacokinetics of cisplatin monotherapy in neonates treated within the first few weeks of life. These data provide a reference point to support clinicians in determining appropriate dosing regimens for neonates and support the implementation of therapeutic drug monitoring in such challenging patients.

Publication metadata

Author(s): Thomas F, Veal GJ, El Balkhi S, Lafont T, Picard N, Brugieres L, Chatelut E, Piguet C

Publication type: Article

Publication status: Published

Journal: Cancer Chemotherapy and Pharmacology

Year: 2018

Volume: 82

Issue: 2

Pages: 361-365

Print publication date: 01/08/2018

Online publication date: 19/06/2018

Acceptance date: 12/06/2018

ISSN (print): 0344-5704

ISSN (electronic): 1432-0843

Publisher: Springer Verlag

URL: https://doi.org/10.1007/s00280-018-3625-5

DOI: 10.1007/s00280-018-3625-5

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