Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: A randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

Elena Aurelia Mazza, A. Brandes, Silvia Zanon, Marica Eoli, Giuseppe Lombardi, Marina Faedi, Enrico Franceschi, Michele Reni

Research output: Contribution to journalArticle

Abstract

Purpose: Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Methods: Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Results: Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75 %, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75 %, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. Conclusion: The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume77
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • Hydroxyurea
  • Imatinib
  • Meningioma
  • Salvage therapy
  • Target therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

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