Journal of Neuro-Oncology

, Volume 83, Issue 1, pp 53–60

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

  • Annick Desjardins
  • 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

DOI: 10.1007/s11060-006-9302-2

Cite this article as:
Desjardins, A., Quinn, J.A., Vredenburgh, J.J. et al. J Neurooncol (2007) 83: 53. doi:10.1007/s11060-006-9302-2

Abstract

Purpose

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.

Results

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.

Conclusion

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

Keywords

Anaplastic astrocytomaAnaplastic oligodendrogliomaGrowth factorImatinib mesylateMalignant gliomaPhase II trialPlatelet-derived

Abbreviations List

AA

anaplastic astrocytoma

AO

anaplastic oligodendroglioma

AOA

anaplastic oligoastrocytoma

CBC

complete blood count

CI

confidence interval

CNS

central nervous system

CR

complete response

DLT

dose-limiting toxicity

EIAED

enzyme inducing anti-epileptic drugs

18FDG PET [18F]

fluorodeoxyglucose positron emission tomography

FDA

Food and Drug Administration

GBM

glioblastoma multiforme

G-CSF

granulocyte colony stimulating factor

GS

gliosarcoma

IRB

institutional review board

ITT

intent-to treat

KM

Kaplan-Meier

KPS

Karnofsky performance status

MG

malignant glioma

MRI

magnetic resonance imaging

MTD

maximum-tolerated dose

OS

overall survival

PD

progressive disease

PFS

progression-free survival

PR

partial response

SD

stable disease

TTP

time to progression

XRT

external beam radiotherapy

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Annick Desjardins
    • 1
  • 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