Targeting VEGF(R) in the treatment of recurrent glioblastoma

Research output: ThesisPhD Thesis

Abstract

Standard treatment for glioblastoma at first diagnosis consists of surgery, followed by radiation therapy and chemotherapy. Despite a significant impact on survival, the tumor will almost inevitably recur. At recurrence, no treatment has demonstrated to prolong overall survival in a randomized clinical trial. Glioblastoma growth is characterized by increased formation of new blood vessels (neo-angiogenesis), a process in which the VEGF(R) receptors and growth factors play an important role. This thesis is built on the results from several clinical trials for patients with recurrent glioblastoma conducted at UZ Brussel. In these trials, the potential of new treatment options targeting the VEGF(R) axis is explored. Sunitinib, a first-in-class small molecule tyrosine kinase inhibitor (TKI) that inhibits VEGF-R, PDGF-R and c-KIT, was investigated as a single agent or in combination with lomustine but failed to show sufficient activity to be developed further. In contrast, experience with bevacizumab in the context of a Belgian Medical Need program in recurrent glioblastoma (including 313 patients), demonstrated that this VEGF-blocking monoclonal antibody has anti-tumor activity with acceptable toxicity and improves progression-free survival, unfortunately without an indication for improved overall survival. Axitinib, a second generation, more specific small molecule VEGF(R) inhibitor, alone or in combination with lomustine, was found to have anti-tumor activity in range with that of bevacizumab. Despite the fact that VEGF(R)-targeted therapy has not become part of standard treatment options for patients with recurrent glioblastoma in the EU, the unique features of these therapeutic agents revealed in our clinical trials have paved the way for combinatorial regimens with immunotherapy that are currently under investigation.
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
Supervisors/Advisors
  • Neyns, Bart, Supervisor
Award date6 Sep 2017
Place of PublicationBrussels
Publication statusPublished - 2017

Keywords

  • chemotherapy

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