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Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 4, pp 1037–1042 | Cite as

Regorafenib in patients with recurrent high-grade astrocytoma

  • Sied Kebir
  • Laurel Rauschenbach
  • Alexander Radbruch
  • Lazaros Lazaridis
  • Teresa Schmidt
  • Ann-Kathrin Stoppek
  • Daniela Pierscianek
  • Martin Stuschke
  • Michael Forsting
  • Ulrich Sure
  • Kathy Keyvani
  • Christoph Kleinschnitz
  • Björn Scheffler
  • Martin GlasEmail author
Original Article – Clinical Oncology

Abstract

Purpose

Antiangiogenic treatment approaches have failed to improve outcome in randomized trials of high-grade astrocytoma. One key mechanism of resistance to antiangiogenic treatment may concern the upregulation of alternative pro-angiogenic pathways. Regorafenib is a potent multikinase inhibitor that may alter some of those pathways. In this retrospective study, we investigated efficacy and radiographic tumor growth patterns of regorafenib in recurrent high-grade astrocytoma.

Methods

We screened for patients with high-grade astrocytoma in whom regorafenib was administered for at least 4 weeks. We assessed treatment efficacy in terms of progression-free survival (PFS), overall survival, and adverse events defined by Common Toxicity Criteria (CTC). In addition, radiographic tumor growth patterns were determined at baseline and recurrence.

Results

A total of 6 patients met eligibility criteria. The number of recurrences prior to regorafenib varied between 2 and 6. Patients were on regorafenib treatment for at least 4 weeks and maximally 14 weeks. Median PFS was 3.5 months and ranged from 2.0 to 4.0 months. Radiographic response was progressive disease in all patients with an objective response rate of 0%. CTC°3 adverse events were observed in all but one patient. The most common radiographic growth pattern was local with no change in growth pattern at recurrence. An infiltrative tumor growth was not induced in any patient.

Conclusions

This retrospective study indicates a very poor performance of regorafenib in recurrent high-grade astrocytoma with a fairly high number of CTC°3 adverse events. In addition, regorafenib does not seem to bear a potential for infiltrative tumor growth promotion.

Keywords

Regorafenib Astrocytoma Glioblastoma High-grade glioma 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this retrospective study, formal consent is not required.

References

  1. Chinot OL, Wick W, MasonW et al (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370(8):709–722CrossRefGoogle Scholar
  2. Das S, Marsden PA (2013) Angiogenesis in glioblastoma. N Engl J Med 369(16):1561–1563CrossRefGoogle Scholar
  3. Gilbert MR, Dignam JJ, Armstrong TS et al (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370(8):699–708CrossRefGoogle Scholar
  4. Hundsberger T, Reardon DA, Wen PY (2017) Angiogenesis inhibitors in tackling recurrent glioblastoma. Expert Rev Anticancer Ther 17(6):507–515CrossRefGoogle Scholar
  5. Lombardi G, De Salvo GL, Brandes AA et al (2019) Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol 20(1):110–119CrossRefGoogle Scholar
  6. Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131(6):803–820CrossRefGoogle Scholar
  7. Norden AD, Young GS, Setayesh K et al (2008) Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 70(10):779–787CrossRefGoogle Scholar
  8. Schaub C, Kebir S, Junold N et al (2018) Tumor growth patterns of MGMT-non-methylated glioblastoma in the randomized GLARIUS trial. J Cancer Res Clin Oncol 144(8):1581–1589CrossRefGoogle Scholar
  9. Uschner FE, Schueller F, Nikolova I et al (2018) The multikinase inhibitor regorafenib decreases angiogenesis and improves portal hypertension. Oncotarget 9(90):36220–36237CrossRefGoogle Scholar
  10. van den Bent MJ, Baumert B, Erridge SC et al (2017) Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet 390(10103):1645–1653CrossRefGoogle Scholar
  11. van den Bent MJ, Klein M, Smits M et al (2018) Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol 19(9):1170–1179CrossRefGoogle Scholar
  12. Weller M, van den Bent M, Tonn JC et al (2017) European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 18(6):e315–e329CrossRefGoogle Scholar
  13. Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28(11):1963–1972CrossRefGoogle Scholar
  14. Wick W, Chinot OL, Bendszus M et al (2016) Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma. Neurooncology 18(10):1434–1441Google Scholar
  15. Wick W, Gorlia T, Bendszus M et al (2017) Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med 377(20):1954–1963CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sied Kebir
    • 1
    • 2
    • 3
    • 4
  • Laurel Rauschenbach
    • 3
    • 4
    • 5
  • Alexander Radbruch
    • 6
  • Lazaros Lazaridis
    • 1
    • 3
    • 4
  • Teresa Schmidt
    • 1
    • 3
    • 4
  • Ann-Kathrin Stoppek
    • 1
    • 3
    • 4
  • Daniela Pierscianek
    • 3
    • 4
    • 5
  • Martin Stuschke
    • 7
  • Michael Forsting
    • 6
  • Ulrich Sure
    • 3
    • 4
    • 5
  • Kathy Keyvani
    • 8
  • Christoph Kleinschnitz
    • 9
  • Björn Scheffler
    • 2
    • 3
    • 4
  • Martin Glas
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Division of Clinical Neurooncology, Department of NeurologyUniversity Hospital Essen, University Duisburg-EssenEssenGermany
  2. 2.DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ)University Hospital EssenEssenGermany
  3. 3.German Cancer Consortium (DKTK), Partner Site University Hospital EssenEssenGermany
  4. 4.West German Cancer Center (WTZ)University Hospital Essen, University Duisburg-EssenEssenGermany
  5. 5.Department of NeurosurgeryUniversity Hospital Essen, University Duisburg-EssenEssenGermany
  6. 6.Institute of Diagnostic and Interventional Radiology and NeuroradiologyUniversity Hospital Essen, University Duisburg-EssenEssenGermany
  7. 7.Department of RadiotherapyUniversity Hospital EssenEssenGermany
  8. 8.Institute of NeuropathologyUniversity of Duisburg-EssenEssenGermany
  9. 9.Department of NeurologyUniversity Hospital Essen, University Duisburg-EssenEssenGermany

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