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Journal of Neuro-Oncology

, Volume 128, Issue 3, pp 463–471 | Cite as

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

  • Kristian W. PajtlerEmail author
  • Stephan Tippelt
  • Nele Siegler
  • Stefanie Reichling
  • Martina Zimmermann
  • Ruth Mikasch
  • Udo Bode
  • Astrid Gnekow
  • Torsten Pietsch
  • Martin Benesch
  • Stefan Rutkowski
  • Gudrun Fleischhack
Clinical Study

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.

Keywords

Ependymoma Medulloblastoma ATRT Relapse Progression Pediatric brain tumors 

Notes

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.

Supplementary material

11060_2016_2133_MOESM1_ESM.pdf (98 kb)
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.
11060_2016_2133_MOESM2_ESM.pdf (192 kb)
Supplementary material 2 (PDF 191 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Kristian W. Pajtler
    • 1
    • 2
    Email author
  • Stephan Tippelt
    • 3
  • Nele Siegler
    • 3
  • Stefanie Reichling
    • 4
  • Martina Zimmermann
    • 4
  • Ruth Mikasch
    • 3
  • Udo Bode
    • 4
  • Astrid Gnekow
    • 5
  • Torsten Pietsch
    • 6
  • Martin Benesch
    • 7
  • Stefan Rutkowski
    • 8
  • Gudrun Fleischhack
    • 3
  1. 1.Division of Pediatric NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Department of Pediatric Oncology, Hematology and ImmunologyUniversity Hospital HeidelbergHeidelbergGermany
  3. 3.Department of Pediatric Oncology and Hematology, Pediatrics IIIUniversity Hospital EssenEssenGermany
  4. 4.Department of Pediatric Hematology and OncologyUniversity of BonnBonnGermany
  5. 5.Hospital for Children and AdolescentsKlinikum AugsburgAugsburgGermany
  6. 6.Institute of NeuropathologyUniversity of BonnBonnGermany
  7. 7.Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent MedicineMedical University of GrazGrazAustria
  8. 8.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg-EppendorfHamburgGermany

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