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Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results

  • Clinical Study - Patient Study
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Abstract

Non-invasive loco-regional electro-hyperthermia (EHT) plus alkylating chemotherapy is occasionally used as salvage treatment in the relapse of patients with high-grade gliomas. Experimental data and retrospective studies suggest potential effects. However, no prospective clinical results are available. We performed a single-center prospective non-controlled single-arm Phase I trial. Main inclusion criteria were recurrent high-grade glioma WHO Grade III or IV, age 18–70, and Karnofsky performance score ≥70. Primary endpoints were dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) with the combined regimen. Groups of 3 or 4 patients were treated 2–5 times a week in a dose-escalation scheme with EHT. Alkylating chemotherapy (ACNU, nimustin) was administered at a dose of 90 mg/m2 on day 1 of 42 days for up to six cycles or until tumor progression (PD) or DLT occurred. Fifteen patients with high-grade gliomas were included. Relevant toxicities were local pain and increased focal neurological signs or intracranial pressure. No DLT occurred. In some patients, the administration of mannitol during EHT or long-term use of corticosteroids was necessary to resolve symptoms. Although some patients showed responses in their primarily treated sites, the pattern of response was not well defined. EHT plus alkylating chemotherapy is tolerable in patients with relapse of high-grade gliomas. Episodes of intracranial pressure were, at least, possibly attributed to EHT but did not cause DLTs. A Phase II trial targeting treatment effects is warranted on the basis of the results raised in this trial.

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Acknowledgements

The trial was supported by an unrestricted educational grant by OncoTherm GmbH, Troisdorf, Germany.

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Authors and Affiliations

  1. Department of Neurology, University of Regensburg Medical School (UKR), Universitätsstrasse 84, 93053, Regensburg, Germany

    Caecilia Wismeth, Christine Dudel, Christina Pascher, Birgit Hirschmann, Christiane Reinert, Ulrich Bogdahn & Peter Hau

  2. Institute of Biophysics and Physical Biochemistry, University of Regensburg, Building PHY 7, 93040, Regensburg, Germany

    Paul Ramm

  3. Institute of Neuropathology, University of Bonn, Sigmund-Freud-Str, 353105, Bonn, Germany

    Torsten Pietsch

  4. Department of Neurosurgery, University Hospital Regensburg, Franz-Josef-Strauß Allee 11, 93053, Regensburg, Germany

    Martin Proescholdt

  5. Institute of Pathology, University of Regensburg, Franz-Josef-Strauß Allee 11, 93053, Regensburg, Germany

    Petra Rümmele

  6. Institute of Neuroradiology, Bezirksklinikum Regensburg, Universitätsstrasse 84, 93053, Regensburg, Germany

    Gerhard Schuierer

Authors
  1. Caecilia Wismeth
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  2. Christine Dudel
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  3. Christina Pascher
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  4. Paul Ramm
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  6. Birgit Hirschmann
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  7. Christiane Reinert
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  8. Martin Proescholdt
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  9. Petra Rümmele
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  10. Gerhard Schuierer
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  11. Ulrich Bogdahn
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  12. Peter Hau
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Corresponding author

Correspondence to Peter Hau.

Additional information

Caecilia Wismeth and Christine Dudel contributed equally to this trial.

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Wismeth, C., Dudel, C., Pascher, C. et al. Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results. J Neurooncol 98, 395–405 (2010). https://doi.org/10.1007/s11060-009-0093-0

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  • DOI: https://doi.org/10.1007/s11060-009-0093-0

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