Display options
Cite
Nijstad AL, Barnett S, Lalmohamed A, et al. Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance. Eur J Cancer. 2021;doi: 10.1016/j.ejca.2021.11.001.
Nijstad, A. L., Barnett, S., Lalmohamed, A., Bérénos, I. M., Parke, E., Carruthers, V., Tweddle, D. A., Kong, J., Zwaan, C. M., Huitema, A. D. R., & Veal, G. J. (2021). Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance. European journal of cancer (Oxford, England : 1990), . https://doi.org/10.1016/j.ejca.2021.11.001
Nijstad, A Laura, et al. "Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance." European journal of cancer (Oxford, England : 1990) vol. (2021). doi: https://doi.org/10.1016/j.ejca.2021.11.001
Nijstad AL, Barnett S, Lalmohamed A, Bérénos IM, Parke E, Carruthers V, Tweddle DA, Kong J, Zwaan CM, Huitema ADR, Veal GJ. Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance. Eur J Cancer. 2021 Dec 02; doi: 10.1016/j.ejca.2021.11.001. Epub 2021 Dec 02. PMID: 34865945.
Copy Download .nbib Format: NLM
Share it on

Eur J Cancer. 2021 Dec 02; doi: 10.1016/j.ejca.2021.11.001. Epub 2021 Dec 02.

Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.

European journal of cancer (Oxford, England : 1990)

A Laura Nijstad, Shelby Barnett, Arief Lalmohamed, Inez M Bérénos, Elizabeth Parke, Vickyanne Carruthers, Deborah A Tweddle, Jordon Kong, C Michel Zwaan, Alwin D R Huitema, Gareth J Veal

Affiliations

  1. Department of Clinical Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands. Electronic address: [email protected].
  2. Newcastle University Centre for Cancer, Newcastle University, NE2 4HH Newcastle Upon Tyne, UK.
  3. Department of Clinical Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands.
  4. Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands.
  5. Newcastle University Centre for Cancer, Newcastle University, NE2 4HH Newcastle Upon Tyne, UK; Great North Children's Hospital, NE1 4LP Newcastle Upon Tyne, UK.
  6. Division of Cancer Sciences, University of Manchester, Manchester, UK.
  7. Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
  8. Department of Clinical Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
  9. Newcastle University Centre for Cancer, Newcastle University, NE2 4HH Newcastle Upon Tyne, UK. Electronic address: [email protected].

PMID: 34865945 DOI: 10.1016/j.ejca.2021.11.001

Abstract

Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of toxicity, mortality, and late effects. Dose optimisation of chemotherapeutics may be an important step to improving outcomes. Body size-based dosing is used for most anticancer drugs used in infants. However, dose regimens are generally not evidence based, and dosing strategies are frequently inconsistent between tumour types and treatment protocols. In this review, we collate available pharmacological evidence supporting dosing regimens in infants for a wide range of cytotoxic drugs. A systematic review was conducted, and available data ranked by a level of evidence (1-5) and a grade of recommendation (A-D) provided on a consensus basis, with recommended dosing approaches indicated as appropriate. For 9 of 29 drugs (busulfan, carboplatin, cyclophosphamide, daunorubicin, etoposide, fludarabine, isotretinoin, melphalan and vincristine), grade A was scored, indicating sufficient pharmacological evidence to recommend a dosing algorithm for infants. For busulfan and carboplatin, sufficient data were available to recommend therapeutic drug monitoring in infants. For eight drugs (actinomycin D, blinatumomab, dinutuximab, doxorubicin, mercaptopurine, pegaspargase, thioguanine and topotecan), some pharmacological evidence was available to guide dosing (graded as B). For the remaining drugs, including commonly used agents such as cisplatin, cytarabine, ifosfamide, and methotrexate, pharmacological evidence for dosing in infants was limited or non-existent: grades C and D were scored for 10 and 2 drugs, respectively. The review provides clinically relevant evidence-based dosing guidance for cytotoxic drugs in neonates and infants.

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

Keywords: Antineoplastic agents; Child; Clinical protocols; Infant; Medical oncology; Paediatrics; Pharmacokinetics; Pharmacology; Therapeutic drug monitoring

Conflict of interest statement

Conflict of interest statement There are no competing interests to declare.

Publication Types