title: Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma.
abstract: OBJECTIVE
  To determine the maximum recommended dose (RD) and pharmacokinetics of Myocet®, a non-pegylated liposomal doxorubicin, in children.
  
  
  METHODS
  Eligible patients were children with refractory high-grade glioma who had received prior chemotherapy and radiotherapy but no anthracyclines. Cohorts of at least three patients each received escalating doses of Myocet® starting at 60 mg/m(2) at 3-week intervals, administered intravenously over 1 h, and then doses were escalated to 75 mg/m(2) corresponding to the adult RD. Periodic blood samples were collected, and plasma doxorubicin and doxorubicinol concentrations were quantified to characterise the pharmacokinetics of Myocet®.
  
  
  RESULTS
  Between October 2010 and January 2013, 13 children aged 6-17 years were treated. In total, 27 courses were administered, at the 60 mg/m(2) dose level in seven patients without dose-limiting toxicity (DLT), and at 75 mg/m(2) in six patients of whom two experienced DLT (grade 4 neutropenia). The most common grade 3-4 toxicities reported for all courses were neutropenia (35 and 38 %, respectively), thrombocytopenia (12 and 4 %, respectively); and grade 3 vomiting, nausea, mucositis, and fever (4 % each). Mean estimates of central volume of distribution at steady state, clearance, and elimination half-life of doxorubicin were 24.8 L, 15 L/h/m(2), and 34.8 h, respectively, with a large interpatient variability.
  
  
  CONCLUSIONS
  The RD of Myocet® administered every 3 weeks to paediatric patients was 60 mg/m(2). The efficacy of Myocet® in paediatric patients with high-grade glioma remains to be determined and should be studied in Phase II trials.
authors.affiliation: Paediatric Oncology Department, Children University Hospital, Allée du Morvan, 54510, Vandœuvre-lès-Nancy Cedex, France, p.chastagner@chu-nancy.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chastagner
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Devictor
authors.forename: Birgit
authors.initials: B
authors.lastname: Geoerger
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aerts
authors.forename: Pierre
authors.initials: P
authors.lastname: Leblond
authors.forename: Didier
authors.initials: D
authors.lastname: Frappaz
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Gentet
authors.forename: Serge
authors.initials: S
authors.lastname: Bracard
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008081:Liposomes; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D017211:Treatment Failure
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin