Journal of Neuro-Oncology

, Volume 102, Issue 3, pp 433–442 | Cite as

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

  • Johannes E. Wolff
  • Rolf-Dieter Kortmann
  • Birte Wolff
  • Torsten Pietsch
  • Ove Peters
  • Hans-Joerg Schmid
  • Stefan Rutkowski
  • Monika Warmuth-Metz
  • Christoph Kramm
Clinical Study - Patient Study


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 gliomas GBM Methotrexate Diffuse intrinsic pontine glioma 


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Johannes E. Wolff
    • 1
    • 2
  • Rolf-Dieter Kortmann
    • 3
  • Birte Wolff
    • 4
  • Torsten Pietsch
    • 5
  • Ove Peters
    • 6
  • Hans-Joerg Schmid
    • 7
  • Stefan Rutkowski
    • 8
  • Monika Warmuth-Metz
    • 9
  • Christoph Kramm
    • 10
  1. 1.Division of Pediatrics, Unit 87The University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Floating Hospital for Children at Tufts Medical CenterBostonUSA
  3. 3.Department of Radiation OncologyUniversity of LeipzigLeipzigGermany
  4. 4.Baylor College of MedicineHoustonUSA
  5. 5.NeuropathologyUniversity of BonnBonnGermany
  6. 6.Klinik St HedwigRegensburgGermany
  7. 7.Department of Pediatric Hematology-OncologyHannoverGermany
  8. 8.Department of Pediatric Hematology-OncologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  9. 9.Neuro-RadiologyUniversity of WürzburgWürzburgGermany
  10. 10.University Children’s Hospital, University of HalleHalleGermany

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