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.
|Number of pages||18|
|Journal||European Journal of Cancer|
|Early online date||2 Dec 2021|
|Publication status||Published - Mar 2022|
Bibliographical noteFunding Information:
This work was supported in part by the National Institute for Health Research (NIHR) Research for Patient Benefit programme ( PB-PG-1216-20032 ), Cancer Research UK ( C9380/A25138 ) and the Experimental Cancer Medicine Centre Network ( C9380/A25169 ). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The position of VC is funded by the Sir Bobby Robson Foundation .
© 2021 The Authors