title: Pharmacotherapies for the treatment of glioblastoma - current evidence and perspectives.
abstract: BACKGROUND
  Glioblastoma, the most common malignant brain tumor, exhibits a poor prognosis with little therapeutic progress in the last decade. Novel treatment strategies beyond the established standard of care with temozolomide-based radiotherapy are urgently needed.
  
  
  METHODS
  We reviewed the literature on glioblastoma with a focus on phase III trials for pharmacotherapies and/or innovative concepts until December 2015.
  
  
  CONCLUSIONS
  In the last decade, phase III trials on novel compounds largely failed to introduce efficacious pharmacotherapies beyond temozolomide in glioblastoma. So far, inhibition of angiogenesis by compounds such as bevacizumab, cediranib, enzastaurin or cilengitide as well as alternative dosing schedules of temozolomide did not prolong survival, neither at primary diagnosis nor at recurrent disease. Promising strategies of pharmacotherapy currently under evaluation represent targeting epidermal growth factor receptor (EGFR) with biomarker-stratified patient populations and immunotherapeutic concepts including checkpoint inhibition and vaccination. The clinical role of the medical device delivering 'tumor-treating fields' in newly diagnosed glioblastoma which prolonged overall survival in a phase III study has remained controversial. After failure of several phase III trials with previously promising agents, improvement of concepts and novel compounds are urgently needed to expand the still limited therapeutic options for the treatment of glioblastoma.
authors.affiliation: a Department of Neurology and Brain Tumor Center , University Hospital and University of Zurich , Zurich , Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Seystahl
authors.affiliation: a Department of Neurology and Brain Tumor Center , University Hospital and University of Zurich , Zurich , Switzerland.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Gramatzki
authors.affiliation: a Department of Neurology and Brain Tumor Center , University Hospital and University of Zurich , Zurich , Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Roth
authors.affiliation: a Department of Neurology and Brain Tumor Center , University Hospital and University of Zurich , Zurich , Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000068258:Bevacizumab / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D012910:Snake Venoms / Q000627:therapeutic use; D000077204:Temozolomide
chemical_list: D012910:Snake Venoms; D000068258:Bevacizumab; C422910:Cilengitide; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Glioblastoma; bevacizumab; clinical trial; immunotherapy; temozolomide