Skip to main content

Advertisement

Log in

Imatinib mesylate treatment of recurrent meningiomas in preselected patients: a retrospective analysis

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. 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

  2. Whittle IR, Smith C, Navoo P, Collie D (2004) Meningiomas. Lancet 363(9420):1535–1543. doi:10.1016/S0140-6736(04)16153-9

    Google Scholar 

  3. 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

    Google Scholar 

  4. 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

    Google Scholar 

  5. 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

    Google Scholar 

  6. 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

  7. Chamberlain MC, Tsao-Wei DD, Groshen S (2004) Temozolomide for treatment-resistant recurrent meningioma. Neurology 62(7):1210–1212

    Article  PubMed  CAS  Google Scholar 

  8. 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

    Article  PubMed  Google Scholar 

  9. Chamberlain MC, Glantz MJ (2008) Interferon-alpha for recurrent World Health Organization grade 1 intracranial meningiomas. Cancer 113(8):2146–2151

    Article  PubMed  CAS  Google Scholar 

  10. 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

    Google Scholar 

  11. 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

    Article  PubMed  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. 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

    Google Scholar 

  14. 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

    Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. 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]

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. 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

    Article  PubMed  CAS  Google Scholar 

  19. 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

    PubMed  CAS  Google Scholar 

  20. Okuda K, Weisberg E, Gilliland DG, Griffin JD (2001) ARG tyrosine kinase activity is inhibited by STI571. Blood 97(8):2440–2448

    Article  PubMed  CAS  Google Scholar 

  21. 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

    Article  PubMed  CAS  Google Scholar 

  22. 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

    Article  PubMed  CAS  Google Scholar 

  23. 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

    Google Scholar 

  24. 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

    Article  PubMed  CAS  Google Scholar 

  25. 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

    Article  PubMed  CAS  Google Scholar 

  26. 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

    Article  PubMed  CAS  Google Scholar 

  27. 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

  28. 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

    Article  PubMed  CAS  Google Scholar 

  29. 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

    Article  PubMed  CAS  Google Scholar 

  30. Newton HB (2007) Hydroxyurea chemotherapy in the treatment of meningiomas. Neurosurg Focus 23(4):E11. doi:10.3171/FOC-07/10/E11

  31. Chamberlain MC, Glantz MJ, Fadul CE (2007) Recurrent meningioma: salvage therapy with long-acting somatostatin analogue. Neurology 69(10):969–973

    Article  PubMed  CAS  Google Scholar 

  32. 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

    Article  PubMed  CAS  Google Scholar 

  33. 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

    Article  PubMed  CAS  Google Scholar 

  34. Wang B, Kruh GD (1996) Subcellular localization of the Arg protein tyrosine kinase. Oncogene 13(1):193–197

    PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christine Marosi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-012-0896-2

Keywords

Navigation