Journal of Neuro-Oncology

, Volume 102, Issue 3, pp 433–442

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


    • Division of Pediatrics, Unit 87The University of Texas M. D. Anderson Cancer Center
    • Floating Hospital for Children at Tufts Medical Center
  • Rolf-Dieter Kortmann
    • Department of Radiation OncologyUniversity of Leipzig
  • Birte Wolff
    • Baylor College of Medicine
  • Torsten Pietsch
    • NeuropathologyUniversity of Bonn
  • Ove Peters
    • Klinik St Hedwig
  • Hans-Joerg Schmid
    • Department of Pediatric Hematology-Oncology
  • Stefan Rutkowski
    • Department of Pediatric Hematology-OncologyUniversity Medical Center Hamburg-Eppendorf
  • Monika Warmuth-Metz
    • Neuro-RadiologyUniversity of Würzburg
  • Christoph Kramm
    • University Children’s Hospital, University of Halle
Clinical Study - Patient Study

DOI: 10.1007/s11060-010-0334-2

Cite this article as:
Wolff, J.E., Kortmann, R., Wolff, B. et al. J Neurooncol (2011) 102: 433. doi:10.1007/s11060-010-0334-2


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.


Pediatric high grade gliomasGBMMethotrexateDiffuse intrinsic pontine glioma

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© Springer Science+Business Media, LLC. 2010