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

  • Clinical Trial Report
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Abstract

Purpose

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/m2 at 3-week intervals, administered intravenously over 1 h, and then doses were escalated to 75 mg/m2 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/m2 dose level in seven patients without dose-limiting toxicity (DLT), and at 75 mg/m2 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/m2, and 34.8 h, respectively, with a large interpatient variability.

Conclusion

The RD of Myocet® administered every 3 weeks to paediatric patients was 60 mg/m2. The efficacy of Myocet® in paediatric patients with high-grade glioma remains to be determined and should be studied in Phase II trials.

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Acknowledgments

We thank Sandrine Pall-Kondolff for helping in data collection.

Author information

Authors and Affiliations

  1. Paediatric Oncology Department, Children University Hospital, Allée du Morvan, 54510, Vandœuvre-lès-Nancy Cedex, France

    Pascal Chastagner

  2. Pharmacokinetic and Toxicology Laboratory, University Hospital la Timone AP-HM, Marseille, France

    Bénédicte Devictor

  3. Paediatric and Adolescent Oncology Department, Gustave Roussy, Villejuif, France

    Birgit Geoerger

  4. Paediatric Adolescent and Young Adults Oncology Department, Curie Institute, Paris, France

    Isabelle Aerts

  5. Paediatric Oncology Department, Oscar Lambret, Lille, France

    Pierre Leblond

  6. Institut d’hémato-oncologie pédiatrique, Lyon, France

    Didier Frappaz

  7. Paediatric Oncology Department, University Children Hospital la Timone, Marseille, France

    Jean-Claude Gentet & Nicolas André

  8. Neuroradiology Department, University Hospital, Nancy, France

    Serge Bracard

  9. INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Aix-Marseille University, Marseille, France

    Nicolas André

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  1. Pascal Chastagner
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Correspondence to Pascal Chastagner.

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Chastagner, P., Devictor, B., Geoerger, B. et al. Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma. Cancer Chemother Pharmacol 76, 425–432 (2015). https://doi.org/10.1007/s00280-015-2781-0

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  • DOI: https://doi.org/10.1007/s00280-015-2781-0

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