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A phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and surgery refractory meningiomas

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Abstract

When surgery and radiation are no longer treatment options, salvage systemic therapy has been used for recurrent meningiomas with little compelling evidence to suggest effectiveness. Patients with surgery and radiation refractory recurrent meningiomas were treated with the oral multifunctional tyrosine kinase inhibitor PTK787/ZK 222584 (PTK787) at a dose of 500 mg twice a day. Each treatment cycle was 4 weeks with MRI done every 8 weeks. Twenty-five patients (14 men; 11 women) with a median age of 59 years and KPS of 80 were treated. Meningioma WHO Grade was I in 2 patients, II in 14 patients and III in 8 patients; 1 patient had a hemangiopericytoma. All patients had prior surgery, external beam radiation therapy or radiosurgery and 11 patients prior systemic chemotherapy. Median number of cycles of PTK 787 administered was 4 (range <1–22). Best response in the 22 evaluable patients was stable disease in 15 (68.2 %). Predominant PTK787 related toxicities included fatigue (60 %), hypertension (24 %) and elevated transaminases (24 %). Grade II patients had a progression free survival (PFS)-6 of 64.3 %, a median PFS of 6.5 months and an overall survival (OS) of 26.0 months; grade III patients had a PFS-6 of 37.5 %, median PFS of 3.6 months and OS 23 months. PTK787 was modestly toxic at the dose of 500 mg administered twice per day. Activity as determined by PFS-6 suggests that targeting PDGF/VEGF pathway warrants further investigation.

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Acknowledgments

This trial was supported by a research grant from Novartis.

Conflict of interest

Jeffrey J. Raizer participated in a Novartis advisory board. Sean A. Grimm, Alfred Rademaker, James P. Chandler, Kenji Muro, Irene Helenowski, Laurie Rice, Katie McCarthy, Sandra K. Johnston, Maciej M. Mrugala, and Marc Chamberlain have no conflicts related to this manuscript.

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Author notes

  1. Sean A. Grimm & Kenji Muro

    Present address: Cadence Health-Central DuPage Hospital Cancer Center, 25 North Winfield Road, Winfield, IL, 60190, USA

  2. Laurie Rice

    Present address: Bend Memorial Clinic, 1501 NE Medical Center Drive, Bend, OR, 97701, USA

Authors and Affiliations

  1. Department of Neurology, Northwestern University, 710 North Lake Shore Drive-Abbott Hall Room 1123, Chicago, IL, 60611, USA

    Jeffrey J. Raizer, Sean A. Grimm, Laurie Rice & Katie McCarthy

  2. Department of Preventative Medicine, Northwestern University, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL, 60611, USA

    Alfred Rademaker & Irene Helenowski

  3. Department of Neurosurgery, Northwestern University, 676 North St. Clair, Suite 2210, Chicago, IL, 60611, USA

    James P. Chandler & Kenji Muro

  4. Department of Neurology, University of Washington/Fred Hutchinson Cancer Research Center, 825 Eastlake Ave E, MS: G-6800, POB 10923, Seattle, WA, 98106, USA

    Sandra K. Johnston, Maciej M. Mrugala & Marc Chamberlain

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Correspondence to Jeffrey J. Raizer.

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Raizer, J.J., Grimm, S.A., Rademaker, A. et al. A phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and surgery refractory meningiomas. J Neurooncol 117, 93–101 (2014). https://doi.org/10.1007/s11060-014-1358-9

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  • DOI: https://doi.org/10.1007/s11060-014-1358-9

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