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High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D Pilot study

  • Clinical Study - Patient Study
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Abstract

We conducted a phase II study to test methotrexate (5 g/m2), as a single agent prior to radiochemotherapy for pediatric high-grade glioma and diffuse intrinsic pontine glioma. Thirty patients (19 male, median age 10.8) were enrolled. Tumors were located as follows: cortex 10, pons 7, other 13. Tumor resection was classified as gross total in 6, subtotal in 6, partial in 4, biopsy in 11 and not performed in 3. WHO grading of the histology was: IV: 11, III: 12 and II: 3. Patients received methotrexate 5 g/m2 in 24-hour infusions on days 1 and 15. Subsequently 54 Gy radiation was administered with simultaneous chemotherapy including cisplatin, etoposide, vincristine and ifosfamide as previously described. Eight 6-weeks cycles of maintenance chemotherapy consisted of vincristine 1.5 mg/m2 on days 1, 8 and 15; lomustine 100 mg/m2 on day 2 and prednisone 40 mg/kg on days 1–17. Event-free survival rates in the whole group of 30 patients were: 43, 20, and 13% after 1, 2 and 5 years, respectively. The response evaluation after methotrexate was available in 19 of the 24 patients who started treatment with measurable disease: CR: 0, PR: 1, SD 18, PD: 0. After radiochemotherapy the response of 24 patients with measurable disease was CR: 1, PR 10, SD 12, PD 1. Both response and event-free survival were superior to the control group of 330 patients treated in various protocols of the same cooperative group. In subgroup analyses the use of dexamethasone during early treatment was linked to poor event free survival. Giving two cycles of high-dose methotrexate prior to radiochemotherapy was feasible, and the approach was taken forward to a randomized phase III trial.

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Acknowledgments

The control group used in this analysis overlaps with previous descriptions. This work was supported by Deutsche Kinderkrebsstiftung, Germany. We thank Sabine Wagner, MD for superb support and helpful discussions.

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Authors and Affiliations

  1. Division of Pediatrics, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Johannes E. Wolff

  2. Floating Hospital for Children at Tufts Medical Center, 755 Washington Street, Boston, MA, 02111, USA

    Johannes E. Wolff

  3. Department of Radiation Oncology, University of Leipzig, Leipzig, Germany

    Rolf-Dieter Kortmann

  4. Baylor College of Medicine, Houston, TX, USA

    Birte Wolff

  5. Neuropathology, University of Bonn, Bonn, Germany

    Torsten Pietsch

  6. Klinik St Hedwig, Regensburg, Germany

    Ove Peters

  7. Department of Pediatric Hematology-Oncology, Hannover, Germany

    Hans-Joerg Schmid

  8. Department of Pediatric Hematology-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Stefan Rutkowski

  9. Neuro-Radiology, University of Würzburg, Würzburg, Germany

    Monika Warmuth-Metz

  10. University Children’s Hospital, University of Halle, Halle, Germany

    Christoph Kramm

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  1. Johannes E. Wolff
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Correspondence to Johannes E. Wolff.

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Wolff, J.E., Kortmann, RD., Wolff, B. et al. High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D Pilot study. J Neurooncol 102, 433–442 (2011). https://doi.org/10.1007/s11060-010-0334-2

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  • DOI: https://doi.org/10.1007/s11060-010-0334-2

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