title: Chemotherapy in newborns and preterm babies.
abstract: The determination of appropriate dosing regimens for the treatment of infants and very young children with cancer represents a major challenge in paediatric oncology. Whereas dose reductions are commonplace for many chemotherapeutics in this patient group, the appropriateness of dose reductions for drugs is unclear when the limited number of published studies reporting on pharmacokinetics in infant patient populations are considered. Developmental physiological changes, potentially impacting significantly on drug disposition, occur throughout childhood, with a number of important changes observed within the first few weeks from birth. The current review focuses on the developmental physiology of preterm babies and infants and the potential impact of physiological changes on drug disposition, clinical response and toxicity. Dose reductions for a number of important anticancer drugs are compared between tumour types and clinical protocols. Where data exist, differences in pharmacokinetics between infants and older children are highlighted. In addition, the impact of confounding factors relating to the availability of appropriate drug formulations and ethical challenges concerning the conduct of clinical pharmacology studies in infant patient populations are addressed. As many currently used drugs are highly likely to be important in the treatment of cancer in infants and young children for the foreseeable future, it would seem advantageous for appropriately planned population pharmacokinetic studies to be carried out in this patient population.
authors.affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Newcastle upon Tyne NE2 4H, UK. Electronic address: g.j.veal@ncl.ac.uk.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Veal
authors.affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Newcastle upon Tyne NE2 4H, UK.
authors.forename: Alan V
authors.initials: AV
authors.lastname: Boddy
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002657:Child Development; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008495:Medical Oncology / Q000639:trends; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D009359:Neonatology / Q000639:trends; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D008727:Methotrexate