Regorafenib in patients with recurrent high-grade astrocytoma

J Cancer Res Clin Oncol. 2019 Apr;145(4):1037-1042. doi: 10.1007/s00432-019-02868-5. Epub 2019 Feb 28.

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: Astrocytoma; Glioblastoma; High-grade glioma; Regorafenib.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use
  • Astrocytoma / blood supply
  • Astrocytoma / diagnostic imaging
  • Astrocytoma / drug therapy*
  • Astrocytoma / pathology
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use*
  • Progression-Free Survival
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Retrospective Studies

Substances

  • Angiogenesis Inhibitors
  • Phenylurea Compounds
  • Pyridines
  • regorafenib