Sied Kebir1,2,3,4, Laurel Rauschenbach3,4,5, Alexander Radbruch6, Lazaros Lazaridis1,3,4, Teresa Schmidt1,3,4, Ann-Kathrin Stoppek1,3,4, Daniela Pierscianek3,4,5, Martin Stuschke7, Michael Forsting6, Ulrich Sure3,4,5, Kathy Keyvani8, Christoph Kleinschnitz9, Björn Scheffler2,3,4, Martin Glas10,11,12,13. 1. Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, 45147, Essen, Germany. 2. DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany. 3. German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany. 4. West German Cancer Center (WTZ), University Hospital Essen, University Duisburg-Essen, Essen, Germany. 5. Department of Neurosurgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 6. Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 7. Department of Radiotherapy, University Hospital Essen, Essen, Germany. 8. Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany. 9. Department of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 10. Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, 45147, Essen, Germany. Martin.Glas@uk-essen.de. 11. DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen, Essen, Germany. Martin.Glas@uk-essen.de. 12. German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany. Martin.Glas@uk-essen.de. 13. West German Cancer Center (WTZ), University Hospital Essen, University Duisburg-Essen, Essen, Germany. Martin.Glas@uk-essen.de.
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.
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.
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