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Intraventricular etoposide safety and toxicity profile in children and young adults with refractory or recurrent malignant brain tumors

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Abstract

Systemic administration of etoposide is effective in treating metastatic, recurrent or refractory brain tumors, but penetration into the cerebrospinal fluid is extremely poor. This study was designed to determine the safety and toxicity profile of intraventricular etoposide administration and was affiliated with the prospective, multicenter, nonblinded, nonrandomized, multi-armed HIT-REZ-97 trial. The study enrolled 68 patients, aged 1.1–34.6 (median age 11 years). Adverse events that could possibly be related to intraventricular etoposide therapy were documented and analyzed. Intraventricular etoposide was simultaneously administered with either oral or intravenous chemotherapy in 426 courses according to three major schedules varying in dosing (0.25–1 mg), frequency of administration (bolus injection, every 12 or 24 h), course duration (5–10 days) and length of interval between courses (2–5 weeks). Potential treatment-related adverse effects included transient headache, seizures, infection of the reservoir, nausea and neuropsychological symptoms. Hematological side effects were not observed. One patient, with history of multiple prior therapies, who received long-term intraventricular and oral etoposide treatment developed acute myeloid leukemia as a secondary malignancy. Overall intraventricular etoposide is well tolerated. The results of this study have warranted a phase II trial to determine the effectiveness of this regimen in disease stages with very limited therapeutic options.

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Acknowledgments

We thank our patients and their families for participation and contribution. We are also grateful to our colleagues and data managers of the participating hospitals for their valuable cooperation. This study was supported by research grants from the German Children Cancer Foundation DKS 99.02/DKS 2002.0.4 and grants to the Reference Centers for Neuroradiology and Neuropathology of the HIT network from the German Children Cancer Foundation. The authors thank K. Astrahantseff for manuscript editing.

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Authors and Affiliations

  1. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

    Kristian W. Pajtler

  2. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Kristian W. Pajtler

  3. Department of Pediatric Oncology and Hematology, Pediatrics III, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany

    Stephan Tippelt, Nele Siegler, Ruth Mikasch & Gudrun Fleischhack

  4. Department of Pediatric Hematology and Oncology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Stefanie Reichling, Martina Zimmermann & Udo Bode

  5. Hospital for Children and Adolescents, Klinikum Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany

    Astrid Gnekow

  6. Institute of Neuropathology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Torsten Pietsch

  7. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria

    Martin Benesch

  8. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Stefan Rutkowski

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  1. Kristian W. Pajtler
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Correspondence to Kristian W. Pajtler.

Electronic supplementary material

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11060_2016_2133_MOESM1_ESM.pdf

Flow chart of the HIT-REZ-97 trial comprising a high-dose, a chemotherapy and a documentation arm. Localized radiotherapy and/or tumor resection were used in all treatment arms.

Supplementary material 2 (PDF 191 kb)

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Pajtler, K.W., Tippelt, S., Siegler, N. et al. Intraventricular etoposide safety and toxicity profile in children and young adults with refractory or recurrent malignant brain tumors. J Neurooncol 128, 463–471 (2016). https://doi.org/10.1007/s11060-016-2133-x

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  • DOI: https://doi.org/10.1007/s11060-016-2133-x

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