Journal of Neuro-Oncology

, Volume 83, Issue 1, pp 53–60 | Cite as

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas

  • Annick DesjardinsEmail author
  • Jennifer A. Quinn
  • James J. Vredenburgh
  • Sith Sathornsumetee
  • Allan H. Friedman
  • James E. Herndon
  • Roger E. McLendon
  • James M. Provenzale
  • Jeremy N. Rich
  • John H. Sampson
  • Sridharan Gururangan
  • Jeannette M. Dowell
  • August Salvado
  • Henry S. Friedman
  • David A. Reardon
Original Paper



Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG).

Patients and method

Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate.


Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1–7) and the median number of prior treatment regimens was 3 (range, 1–8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses.


Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.


Anaplastic astrocytoma Anaplastic oligodendroglioma Growth factor Imatinib mesylate Malignant glioma Phase II trial Platelet-derived 

Abbreviations List


anaplastic astrocytoma


anaplastic oligodendroglioma


anaplastic oligoastrocytoma


complete blood count


confidence interval


central nervous system


complete response


dose-limiting toxicity


enzyme inducing anti-epileptic drugs

18FDG PET [18F]

fluorodeoxyglucose positron emission tomography


Food and Drug Administration


glioblastoma multiforme


granulocyte colony stimulating factor




institutional review board


intent-to treat




Karnofsky performance status


malignant glioma


magnetic resonance imaging


maximum-tolerated dose


overall survival


progressive disease


progression-free survival


partial response


stable disease


time to progression


external beam radiotherapy


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Annick Desjardins
    • 1
    Email author
  • Jennifer A. Quinn
    • 1
  • James J. Vredenburgh
    • 1
  • Sith Sathornsumetee
    • 1
  • Allan H. Friedman
    • 2
  • James E. Herndon
    • 4
  • Roger E. McLendon
    • 5
  • James M. Provenzale
    • 3
  • Jeremy N. Rich
    • 1
  • John H. Sampson
    • 2
  • Sridharan Gururangan
    • 6
  • Jeannette M. Dowell
    • 4
  • August Salvado
    • 7
  • Henry S. Friedman
    • 2
    • 6
  • David A. Reardon
    • 2
    • 6
  1. 1.Department of Medicine, Division of NeurologyThe Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical CenterDurhamUSA
  2. 2.Department of SurgeryThe Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical CenterDurhamUSA
  3. 3.Department of RadiologyThe Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical CenterDurhamUSA
  4. 4.Cancer Center BiostatisticsThe Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical CenterDurhamUSA
  5. 5.Department of PathologyThe Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical CenterDurhamUSA
  6. 6.Department of PediatricsThe Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical CenterDurhamUSA
  7. 7.Novartis PharmaceuticalsEast HanoverUSA

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