title: Carboplatin therapeutic monitoring in preterm and full-term neonates.
abstract: BACKGROUND
  Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life.
  
  
  METHODS
  Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8 year period. Carboplatin was administered over 3 days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8 mg/ml min.
  
  
  RESULTS
  AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1 ml/min and from 7.2 to 16.5 ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity.
  
  
  CONCLUSIONS
  The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment.
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: G.J.Veal@ncl.ac.uk.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Veal
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Errington
authors.affiliation: Alder Hey Children's NHS Trust, Liverpool L12 2AP, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hayden
authors.affiliation: Birmingham Children's Hospital, Birmingham B4 6NH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hobin
authors.affiliation: Royal Hospital for Sick Children, Glasgow G3 8SJ, UK.
authors.forename: Dermot
authors.initials: D
authors.lastname: Murphy
authors.affiliation: Bristol Royal Hospital for Children, Bristol BS2 8BJ, UK.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Dommett
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Great North Children's Hospital, Newcastle upon Tyne NE1 4LP, UK.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Tweddle
authors.affiliation: Birmingham Children's Hospital, Birmingham B4 6NH, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Jenkinson
authors.affiliation: Leeds General Infirmary, Leeds LS1 3EX, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Picton
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D009447:Neuroblastoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011237:Predictive Value of Tests; D012074:Remission Induction; D012175:Retinoblastoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D047929:Term Birth; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin
keywords: Carboplatin; Chemotherapy; Neonates; Neuroblastoma; Retinoblastoma; Therapeutic drug monitoring