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

Jeffrey J. Raizer, Sean A. Grimm, Alfred Rademaker, James P. Chandler, Kenji Muro, Irene Helenowski, Laurie Rice, Katie McCarthy, Sandra K. Johnston, Maciej M. Mrugala, Marc Chamberlain

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalJournal of neuro-oncology
Volume117
Issue number1
DOIs
StatePublished - Jan 1 2014

    Fingerprint

Keywords

  • Chemotherapy
  • Meningioma
  • PDGF
  • PTK787
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Raizer, J. J., Grimm, S. A., Rademaker, A., Chandler, J. P., Muro, K., Helenowski, I., Rice, L., McCarthy, K., Johnston, S. K., Mrugala, M. M., & Chamberlain, M. (2014). A phase II trial of PTK787/ZK 222584 in recurrent or progressive radiation and surgery refractory meningiomas. Journal of neuro-oncology, 117(1), 93-101. https://doi.org/10.1007/s11060-014-1358-9