title: 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).
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Oncology Unit, Department of Oncology, IRCCS Ospedale, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Mazza
authors.affiliation: Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL of Bologna - IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Brandes
authors.affiliation: Medical Oncology Unit, Department of Oncology, IRCCS Ospedale, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zanon
authors.affiliation: Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Eoli
authors.affiliation: Department of Experimental and Clinical Oncology, Medical Oncology 1, Veneto Institute of Oncology-IRCCS, Padua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Faedi
authors.affiliation: Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL of Bologna - IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Franceschi
authors.affiliation: Medical Oncology Unit, Department of Oncology, IRCCS Ospedale, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy. reni.michele@hsr.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000627:therapeutic use; D000068877:Imatinib Mesylate / Q000008:administration & dosage; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008579:Meningioma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000068877:Imatinib Mesylate; D006918:Hydroxyurea
keywords: Hydroxyurea; Imatinib; Meningioma; Salvage therapy; Target therapy