Skip to main content
Top
Published in: Cancer Chemotherapy and Pharmacology 2/2018

01-08-2018 | Short Communication

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

Authors: Fabienne Thomas, Gareth J. Veal, Souleiman El Balkhi, Thierry Lafont, Nicolas Picard, Laurence Brugières, Etienne Chatelut, Christophe Piguet

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2018

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Meyers RL, Maibach R, Hiyama E et al (2017) Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children’s Hepatic tumors International Collaboration. Lancet Oncol 18:122–131CrossRefPubMed Meyers RL, Maibach R, Hiyama E et al (2017) Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children’s Hepatic tumors International Collaboration. Lancet Oncol 18:122–131CrossRefPubMed
4.
go back to reference Zsiros J, Brugieres L, Brock P et al (2013) Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol 14:834–842CrossRefPubMedPubMedCentral Zsiros J, Brugieres L, Brock P et al (2013) Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol 14:834–842CrossRefPubMedPubMedCentral
6.
go back to reference Veal GJ, Errington J, Sastry J et al (2016) Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens. Cancer Chemother Pharmacol 77:685–692CrossRefPubMedPubMedCentral Veal GJ, Errington J, Sastry J et al (2016) Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens. Cancer Chemother Pharmacol 77:685–692CrossRefPubMedPubMedCentral
7.
go back to reference Perilongo G, Maibach R, Shafford E et al (2009) Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med 361:1662–1670CrossRefPubMed Perilongo G, Maibach R, Shafford E et al (2009) Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med 361:1662–1670CrossRefPubMed
8.
go back to reference LeRoy AF, Wehling ML, Sponseller HL et al (1977) Analysis of platinum in biological materials by flameless atomic absorption spectrophotometry. Biochem Med 18:184–191CrossRefPubMed LeRoy AF, Wehling ML, Sponseller HL et al (1977) Analysis of platinum in biological materials by flameless atomic absorption spectrophotometry. Biochem Med 18:184–191CrossRefPubMed
9.
go back to reference Burger H, Loos WJ, Eechoute K et al (2011) Drug transporters of platinum-based anticancer agents and their clinical significance. Drug Resist Updat 14:22–34CrossRefPubMed Burger H, Loos WJ, Eechoute K et al (2011) Drug transporters of platinum-based anticancer agents and their clinical significance. Drug Resist Updat 14:22–34CrossRefPubMed
10.
go back to reference Sweeney DE, Vallon V, Rieg T et al (2011) Functional maturation of drug transporters in the developing, neonatal, and postnatal kidney. Mol Pharmacol 80:147–154CrossRefPubMedPubMedCentral Sweeney DE, Vallon V, Rieg T et al (2011) Functional maturation of drug transporters in the developing, neonatal, and postnatal kidney. Mol Pharmacol 80:147–154CrossRefPubMedPubMedCentral
11.
go back to reference Lickteig AJ, Cheng X, Augustine LM et al (2008) Tissue distribution, ontogeny and induction of the transporters Multidrug and toxin extrusion (MATE) 1 and MATE2 mRNA expression levels in mice. Life Sci 83:59–64CrossRefPubMedPubMedCentral Lickteig AJ, Cheng X, Augustine LM et al (2008) Tissue distribution, ontogeny and induction of the transporters Multidrug and toxin extrusion (MATE) 1 and MATE2 mRNA expression levels in mice. Life Sci 83:59–64CrossRefPubMedPubMedCentral
12.
go back to reference Bardin C, Veal G, Paci A et al (2014) Therapeutic drug monitoring in cancer—are we missing a trick? Eur J Cancer Oxf Engl 1990 50:2005–2009 Bardin C, Veal G, Paci A et al (2014) Therapeutic drug monitoring in cancer—are we missing a trick? Eur J Cancer Oxf Engl 1990 50:2005–2009
Metadata
Title
Therapeutic drug monitoring and dose adaptation of cisplatin in a newborn with hepatoblastoma: a case report
Authors
Fabienne Thomas
Gareth J. Veal
Souleiman El Balkhi
Thierry Lafont
Nicolas Picard
Laurence Brugières
Etienne Chatelut
Christophe Piguet
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3625-5

Other articles of this Issue 2/2018

Cancer Chemotherapy and Pharmacology 2/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine