Abstract
Some unresectable and symptomatic meningiomas recur after conventional radiation therapy or stereotactic radiosurgery and are a therapeutic challenge. Evidence-based data from medical therapy for patients with recurrent meningioma can be deemed insufficient. Because of the prevalent expression of PDGF receptors in meningiomas, the tyrosine kinase imatinib mesylate has attracted interest as a treatment option for this patient group. In this retrospective study we analyzed 18 patients with recurrent meningiomas who were treated at our institution between 1996 and 2008. Nine patients with positive immunohistochemical staining of at least one of the PDGF receptors were given a daily oral dose of 400 mg imatinib mesylate as first, second, or third-line systemic therapy. Immunohistochemical staining was performed on formalin-fixed and paraffin-embedded tumor tissue with antibodies against PDGFR-α and β, c-Kit, Arg, and c-Abl. Imatinib mesylate at a dose of 400–800 mg/day was well tolerated. Of nine patients treated with imatinib, seven had stable disease and two had progressed at the first scan after three months. We observed no complete or partial responses, although prolonged disease stabilization with progression-free survival of 66.7 % at six months was observed. Overall median progression-free survival was 16 months. We conclude that single-agent imatinib mesylate might be a well-tolerated therapeutic option with high achievement of disease stabilization for preselected patients with recurrent meningiomas. Because of the small cohort, non-randomized design, and highly diverse patient population, we propose future prospective studies to validate our results.
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Central Brain Tumor Registry of the United States (2010) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2006. http://www.cbtrus.org/reports/reports.html. Accessed 12 October 2010
Whittle IR, Smith C, Navoo P, Collie D (2004) Meningiomas. Lancet 363(9420):1535–1543. doi:10.1016/S0140-6736(04)16153-9
Wen PY, Quant E, Drappatz J, Beroukhim R, Norden AD (2010) Medical therapies for meningiomas. J Neurooncol 99(3):365–378. doi:10.1007/s11060-010-0349-8
Sioka C, Kyritsis AP (2009) Chemotherapy, hormonal therapy, and immunotherapy for recurrent meningiomas. J Neurooncol 92(1):1–6. doi:10.1007/s11060-008-9734-y
Marosi C, Hassler M, Roessler K, Reni M, Sant M, Mazza E, Vecht C (2008) Meningioma. Crit Rev Oncol Hematol 67(2):153–171. doi:10.1016/j.critrevonc.2008.01.010
Rockhill J, Mrugala M, Chamberlain MC (2007) Intracranial meningiomas: an overview of diagnosis and treatment. Neurosurg Focus 23(4):E1. doi:10.3171/FOC-07/10/E1
Chamberlain MC, Tsao-Wei DD, Groshen S (2004) Temozolomide for treatment-resistant recurrent meningioma. Neurology 62(7):1210–1212
Arena S, Barbieri F, Thellung S, Pirani P, Corsaro A, Villa V, Dadati P, Dorcaratto A, Lapertosa G, Ravetti JL, Spaziante R, Schettini G, Florio T (2004) Expression of somatostatin receptor mRNA in human meningiomas and their implication in in vitro antiproliferative activity. J Neurooncol 66(1–2):155–166
Chamberlain MC, Glantz MJ (2008) Interferon-alpha for recurrent World Health Organization grade 1 intracranial meningiomas. Cancer 113(8):2146–2151
Chamberlain MC, Johnston SK (2012) Hydroxyurea for recurrent surgery and radiation refractory meningioma: a retrospective case series. J Neurooncol 107(2):315–321. doi:10.1007/s11060-011-0541-5
Chargari C, Vedrine L, Bauduceau O, Le Moulec S, Ceccaldi B, Magne N (2008) Reappraisal of the role of endocrine therapy in meningioma management. Endocr Relat Cancer 15(4):931–941
Grunberg SM, Weiss MH, Russell CA, Spitz IM, Ahmadi J, Sadun A, Sitruk-Ware R (2006) Long-term administration of mifepristone (RU486): clinical tolerance during extended treatment of meningioma. Cancer Invest 24(8):727–733
Johnson DR, Kimmel DW, Burch PA, Cascino TL, Giannini C, Wu W, Buckner JC (2011) Phase II study of subcutaneous octreotide in adults with recurrent or progressive meningioma and meningeal hemangiopericytoma. Neuro Oncol 13(5):530–535. doi:10.1093/neuonc/nor044
Puchner MJ, Hans VH, Harati A, Lohmann F, Glas M, Herrlinger U (2010) Bevacizumab-induced regression of anaplastic meningioma. Ann Oncol 21(12):2445–2446. doi:10.1093/annonc/mdq634
Johnson MD, Sade B, Milano MT, Lee JH, Toms SA (2008) New prospects for management and treatment of inoperable and recurrent skull base meningiomas. J Neurooncol 86(1):109–122
Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B, Goldman J, O’Brien SG, Russell N, Fischer T, Ottmann O, Cony-Makhoul P, Facon T, Stone R, Miller C, Tallman M, Brown R, Schuster M, Loughran T, Gratwohl A, Mandelli F, Saglio G, Lazzarino M, Russo D, Baccarani M, Morra E (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346(9):645–652. doi:10.1056/NEJMoa011573346/9/645 [pii]
Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2(5):561–566
Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344(14):1031–1037. doi:10.1056/NEJM200104053441401
Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ (2000) Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96(3):925–932
Okuda K, Weisberg E, Gilliland DG, Griffin JD (2001) ARG tyrosine kinase activity is inhibited by STI571. Blood 97(8):2440–2448
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347(7):472–480
Wang JL, Nister M, Hermansson M, Westermark B, Ponten J (1990) Expression of PDGF beta-receptors in human meningioma cells. Int J Cancer 46(5):772–778
Todo T, Adams EF, Fahlbusch R, Dingermann T, Werner H (1996) Autocrine growth stimulation of human meningioma cells by platelet-derived growth factor. J Neurosurg 84(5):852–858; discussion 858–859. doi:10.3171/jns.1996.84.5.0852
Maxwell M, Galanopoulos T, Hedley-Whyte ET, Black PM, Antoniades HN (1990) Human meningiomas co-express platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products. Int J Cancer 46(1):16–21
Johnson MD, Woodard A, Kim P, Frexes-Steed M (2001) Evidence for mitogen-associated protein kinase activation and transduction of mitogenic signals by platelet-derived growth factor in human meningioma cells. J Neurosurg 94(2):293–300. doi:10.3171/jns.2001.94.2.0293
Black PM, Carroll R, Glowacka D, Riley K, Dashner K (1994) Platelet-derived growth factor expression and stimulation in human meningiomas. J Neurosurg 81(3):388–393. doi:10.3171/jns.1994.81.3.0388
Wen PY, Yung WK, Lamborn KR, Norden AD, Cloughesy TF, Abrey LE, Fine HA, Chang SM, Robins HI, Fink K, Deangelis LM, Mehta M, Di Tomaso E, Drappatz J, Kesari S, Ligon KL, Aldape K, Jain RK, Stiles CD, Egorin MJ, Prados MD (2009) Phase II study of imatinib mesylate for recurrent meningiomas (North American brain tumor consortium study 01–08). Neuro Oncol 11(6):853–860. doi:10.1215/15228517-2009-010
Reardon DA, Norden AD, Desjardins A, Vredenburgh JJ, Herndon JE 2nd, Coan A, Sampson JH, Gururangan S, Peters KB, McLendon RE, Norfleet JA, Lipp ES, Drappatz J, Wen PY, Friedman HS (2012) Phase II study of Gleevec(R) plus hydroxyurea (HU) in adults with progressive or recurrent meningioma. J Neurooncol 106(2):409–415. doi:10.1007/s11060-011-0687-1
Haberler C, Gelpi E, Marosi C, Rossler K, Birner P, Budka H, Hainfellner JA (2006) Immunohistochemical analysis of platelet-derived growth factor receptor-alpha, -beta, c-kit, c-abl, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy. J Neurooncol 76(2):105–109. doi:10.1007/s11060-005-4570-9
Newton HB (2007) Hydroxyurea chemotherapy in the treatment of meningiomas. Neurosurg Focus 23(4):E11. doi:10.3171/FOC-07/10/E11
Chamberlain MC, Glantz MJ, Fadul CE (2007) Recurrent meningioma: salvage therapy with long-acting somatostatin analogue. Neurology 69(10):969–973
Kruh GD, Perego R, Miki T, Aaronson SA (1990) The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases. Proc Natl Acad Sci USA 87(15):5802–5806
Miller AL, Wang Y, Mooseker MS, Koleske AJ (2004) The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. J Cell Biol 165(3):407–419
Wang B, Kruh GD (1996) Subcellular localization of the Arg protein tyrosine kinase. Oncogene 13(1):193–197
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Horak, P., Wöhrer, A., Hassler, M. et al. Imatinib mesylate treatment of recurrent meningiomas in preselected patients: a retrospective analysis. J Neurooncol 109, 323–330 (2012). https://doi.org/10.1007/s11060-012-0896-2
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DOI: https://doi.org/10.1007/s11060-012-0896-2