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Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma

  • Clinical Study – Patient Study
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Abstract

We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.

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Abbreviations

OS:

Overall survival

PFS:

Progression-free survival

mg:

Milligram

EIAEDs:

CYP3A enzyme inducing anti-epileptic drugs

KPS:

Karnofsky performance status

PD:

Progressive disease

STR:

Stereotactic radiosurgery

XRT:

External beam radiotherapy

CNS:

Central nervous system

PDGFR:

Platelet derived growth factor receptor

STR:

Subtotal resection

SRS:

Stereotactic radiosurgery

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Acknowledgments

This study was financially supported by grants P50 NS20023 and R37 CA011898 from NIH, Department of Health and Human Services, Bethesda, Maryland and a research grant from Novartis Pharmaceuticals. The investigators wish to thank Wendy Gentry for her assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Duke University Medical Center, Box 3624, Durham, NC, 27710, USA

    David A. Reardon

  2. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    David A. Reardon, Annick Desjardins, James J. Vredenburgh, John H. Sampson, Sridharan Gururangan, Katherine B. Peters, Julie A. Norfleet, Eric S. Lipp & Henry S. Friedman

  3. Department of Pediatrics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    David A. Reardon, Sridharan Gururangan & Henry S. Friedman

  4. Department of Medicine, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    Annick Desjardins, James J. Vredenburgh & Katherine B. Peters

  5. Department of Biostatistics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    James E. Herndon II & April Coan

  6. Departments of Neurobiology and Pathology, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    Roger E. McLendon

  7. The Center for Neuro-Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA, 02115, USA

    Andrew D. Norden, Jan Drappatz & Patrick Y. Wen

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  1. David A. Reardon
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  2. Andrew D. Norden
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  8. Sridharan Gururangan
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  9. Katherine B. Peters
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  10. Roger E. McLendon
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  14. Patrick Y. Wen
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  15. Henry S. Friedman
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Correspondence to David A. Reardon.

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Reardon, D.A., Norden, A.D., Desjardins, A. et al. Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma. J Neurooncol 106, 409–415 (2012). https://doi.org/10.1007/s11060-011-0687-1

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  • DOI: https://doi.org/10.1007/s11060-011-0687-1

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