Elena Mazza1, Alba Brandes2, Silvia Zanon1, Marika Eoli3, Giuseppe Lombardi4, Marina Faedi5, Enrico Franceschi2, Michele Reni6. 1. Medical Oncology Unit, Department of Oncology, IRCCS Ospedale, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy. 2. Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL of Bologna - IRCCS Institute of Neurological Sciences, Bologna, Italy. 3. Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy. 4. Department of Experimental and Clinical Oncology, Medical Oncology 1, Veneto Institute of Oncology-IRCCS, Padua, Italy. 5. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 6. Medical Oncology Unit, Department of Oncology, IRCCS Ospedale, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy. reni.michele@hsr.it.
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.
RCT Entities:
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.
Authors: Richard G Everson; Yuuri Hashimoto; Jacob L Freeman; Tiffany R Hodges; Jason Huse; Shouhao Zhou; Joanne Xiu; David Spetzler; Nader Sanai; Lyndon Kim; Santosh Kesari; Andrew Brenner; Franco De Monte; Amy Heimberger; Shaan M Raza Journal: J Neurooncol Date: 2018-05-30 Impact factor: 4.130
Authors: Matthias Preusser; Antonio Silvani; Emilie Le Rhun; Riccardo Soffietti; Giuseppe Lombardi; Juan Manuel Sepulveda; Petter Brandal; Lucy Brazil; Alice Bonneville-Levard; Veronique Lorgis; Elodie Vauleon; Jacoline Bromberg; Sara Erridge; Alison Cameron; Florence Lefranc; Paul M Clement; Sarah Dumont; Marc Sanson; Charlotte Bronnimann; Carmen Balaná; Niklas Thon; Joanne Lewis; Maximilian J Mair; Philipp Sievers; Julia Furtner; Josef Pichler; Jordi Bruna; Francois Ducray; Jaap C Reijneveld; Christian Mawrin; Martin Bendszus; Christine Marosi; Vassilis Golfinopoulos; Corneel Coens; Thierry Gorlia; Michael Weller; Felix Sahm; Wolfgang Wick Journal: Neuro Oncol Date: 2022-05-04 Impact factor: 13.029
Authors: Asma Bashir; Mark Bitsch Vestergaard; Tina Binderup; Helle Broholm; Lisbeth Marner; Morten Ziebell; Kåre Fugleholm; Tiit Mathiesen; Andreas Kjær; Ian Law Journal: Eur J Nucl Med Mol Imaging Date: 2020-03-13 Impact factor: 9.236
Authors: Leland Rogers; Peixin Zhang; Michael A Vogelbaum; Arie Perry; Lynn S Ashby; Jignesh M Modi; Anthony M Alleman; James Galvin; David Brachman; Joseph M Jenrette; John De Groot; Joseph A Bovi; Maria Werner-Wasik; Jonathan P S Knisely; Minesh P Mehta Journal: J Neurosurg Date: 2017-10-06 Impact factor: 5.115