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Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma

Chastagner, Pascal ; Devictor, Bénédicte ; Geoerger, Birgit ; Aerts, Isabelle ; Leblond, Pierre ; Frappaz, Didier ; Gentet, Jean-Claude ; Bracard, Serge ; André, Nicolas

Cancer Chemotherapy and Pharmacology, 2015, Vol.76(2), pp.425-432 [Periódico revisado por pares]

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  • Título:
    Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma
  • Autor: Chastagner, Pascal ; Devictor, Bénédicte ; Geoerger, Birgit ; Aerts, Isabelle ; Leblond, Pierre ; Frappaz, Didier ; Gentet, Jean-Claude ; Bracard, Serge ; André, Nicolas
  • Assuntos: Liposomal doxorubicin ; Myocet ; Pharmacokinetic ; Children ; Phase I trial ; High-grade glioma
  • É parte de: Cancer Chemotherapy and Pharmacology, 2015, Vol.76(2), pp.425-432
  • Descrição: Byline: Pascal Chastagner (1), Benedicte Devictor (2), Birgit Geoerger (3), Isabelle Aerts (4), Pierre Leblond (5), Didier Frappaz (6), Jean-Claude Gentet (7), Serge Bracard (8), Nicolas Andre (7,9) Keywords: Liposomal doxorubicin; Myocet.sup.[R]; Pharmacokinetic; Children; Phase I trial; High-grade glioma Abstract: Purpose To determine the maximum recommended dose (RD) and pharmacokinetics of Myocet.sup.[R], 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.sup.[R] starting at 60 mg/m.sup.2 at 3-week intervals, administered intravenously over 1 h, and then doses were escalated to 75 mg/m.sup.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.sup.[R]. 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.sup.2 dose level in seven patients without dose-limiting toxicity (DLT), and at 75 mg/m.sup.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.sup.2, and 34.8 h, respectively, with a large interpatient variability. Conclusion The RD of Myocet.sup.[R] administered every 3 weeks to paediatric patients was 60 mg/m.sup.2. The efficacy of Myocet.sup.[R] in paediatric patients with high-grade glioma remains to be determined and should be studied in Phase II trials. Author Affiliation: (1) Paediatric Oncology Department, Children University Hospital, Allee du Morvan, 54510, VandAuvre-les-Nancy Cedex, France (2) Pharmacokinetic and Toxicology Laboratory, University Hospital la Timone AP-HM, Marseille, France (3) Paediatric and Adolescent Oncology Department, Gustave Roussy, Villejuif, France (4) Paediatric Adolescent and Young Adults Oncology Department, Curie Institute, Paris, France (5) Paediatric Oncology Department, Oscar Lambret, Lille, France (6) Institut d'hemato-oncologie pediatrique, Lyon, France (7) Paediatric Oncology Department, University Children Hospital la Timone, Marseille, France (8) Neuroradiology Department, University Hospital, Nancy, France (9) INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Aix-Marseille University, Marseille, France Article History: Registration Date: 16/05/2015 Received Date: 27/04/2015 Accepted Date: 18/05/2015 Online Date: 27/06/2015
  • Idioma: Inglês

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