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

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Abstract

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.

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Abbreviations

MG:

Malignant glioma

ITT:

Intent-to treat

ANC:

Absolute neutrophil count

AST:

Aspartate aminotransferase

CNS:

Central nervous system

CR:

Complete response

GBM:

Glioblastoma

KPS:

Karnofsky performance status

ORR:

Overall response rate

OS:

Overall survival

PD:

Progressive disease

PFS:

Progression-free survival

PR:

Partial response

SD:

Stable disease

VEGF:

Vascular endothelial growth factor

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Acknowledgments

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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Correspondence to David A. Reardon.

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Reardon, D.A., Desjardins, A., Peters, K. et al. Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. J Neurooncol 103, 371–379 (2011). https://doi.org/10.1007/s11060-010-0403-6

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