Journal of Neuro-Oncology

, Volume 103, Issue 2, pp 371–379 | Cite as

Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy

  • David A. ReardonEmail author
  • Annick Desjardins
  • Katherine Peters
  • Sridharan Gururangan
  • John Sampson
  • Jeremy N. Rich
  • Roger McLendon
  • James E. HerndonII
  • Jennifer Marcello
  • Stevie Threatt
  • Allan H. Friedman
  • James J. Vredenburgh
  • Henry S. Friedman
Clinical Study – Patient Study


We evaluated the efficacy of metronomic etoposide or temozolomide administered with bevacizumab among recurrent glioblastoma (GBM) patients who progressed on prior bevacizumab therapy in a phase 2, open-label, two-arm trial. Twenty-three patients received bevacizumab (10 mg/kg) every 2 weeks with either oral etoposide (50 mg/m2) daily for 21 consecutive days each month or daily temozolomide (50 mg/m2). The primary endpoint was 6-month progression-free survival (PFS-6) and secondary endpoints included safety and overall survival. Both the etoposide and temozolomide arms of the study closed at the interim analysis due to lack of adequate anti-tumor activity. No radiographic responses were observed. Although 12 patients (52%) achieved stable disease, PFS-6 was 4.4% and the median PFS was 7.3 weeks. The only grade 4 adverse event was reversible neutropenia. Grade 3 toxicities included fatigue (n = 2) and infection (n = 1). Metronomic etoposide or temozolomide is ineffective when administered with bevacizumab among recurrent GBM patients who have progressed on prior bevacizumab therapy. Alternative treatment strategies remain critically needed for this indication.


Glioblastoma Angiogenesis Bevacizumab Vascular endothelial growth factor Metronomic chemotherapy 



Malignant glioma


Intent-to treat


Absolute neutrophil count


Aspartate aminotransferase


Central nervous system


Complete response




Karnofsky performance status


Overall response rate


Overall survival


Progressive disease


Progression-free survival


Partial response


Stable disease


Vascular endothelial growth factor



This work was supported by NIH Grants 5P50-NS-20023 and 5 R37 CA11898; NIH Grant MO1 RR 30, GCRC Program, NCRR; and NCI SPORE 1 P20 CA096890; and a grant from Genentech Pharmaceuticals.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • David A. Reardon
    • 1
    • 2
    Email author
  • Annick Desjardins
    • 3
  • Katherine Peters
    • 3
  • Sridharan Gururangan
    • 1
    • 2
  • John Sampson
    • 1
  • Jeremy N. Rich
    • 3
  • Roger McLendon
    • 4
  • James E. HerndonII
    • 5
  • Jennifer Marcello
    • 5
  • Stevie Threatt
    • 1
  • Allan H. Friedman
    • 1
  • James J. Vredenburgh
    • 3
  • Henry S. Friedman
    • 1
    • 2
  1. 1.Departments of SurgeryThe Preston Robert Tisch Brain Tumor Center, Duke University Medical CenterDurhamUSA
  2. 2.Departments of PediatricsThe Preston Robert Tisch Brain Tumor Center, Duke University Medical CenterDurhamUSA
  3. 3.Departments of MedicineThe Preston Robert Tisch Brain Tumor Center, Duke University Medical CenterDurhamUSA
  4. 4.Departments of PathologyThe Preston Robert Tisch Brain Tumor Center, Duke University Medical CenterDurhamUSA
  5. 5.Cancer Center BiostatisticsThe Preston Robert Tisch Brain Tumor Center, Duke University Medical CenterDurhamUSA

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