title: Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme.
abstract: BACKGROUND
  The current study was conducted to evaluate the efficacy of sorafenib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, when added to standard radiotherapy and temozolomide in the first-line treatment of patients with glioblastoma multiforme.
  
  
  METHODS
  After initial surgical resection or biopsy, patients with newly diagnosed glioblastoma multiforme received concurrent radiotherapy (2.0 grays [Gy]/day; total dose, 60 Gy) and temozolomide (at a dose of 75 mg/m2 orally daily), followed by 6 months of maintenance therapy with temozolomide (at a dose of 150 mg/m2 orally on Days 1-5 every 28 days) and sorafenib (at a dose of 400 mg orally twice daily). Patients were re-evaluated every 2 months; the primary endpoint of the trial was progression-free survival (PFS).
  
  
  RESULTS
  A total of 47 patients were treated; 34 had undergone previous debulking surgery. Nineteen patients withdrew from treatment before the initiation of maintenance therapy with temozolomide and sorafenib (12 because of early tumor progression). Twenty-eight patients (60% of enrolled patients) received 4 months of maintenance therapy with temozolomide and sorafenib, and 9 patients (19%) completed the planned 6 months of maintenance therapy. The median PFS for the entire group was 6 months (95% confidence interval [95% CI], 3.7-7 months), with a 1-year PFS rate of 16%. The median overall survival was 12 months (95%CI, 7.2-16 months). Maintenance therapy with temozolomide and sorafenib was found to be well tolerated by most patients, with no grade 3/4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) reported to occur in >10% of patients.
  
  
  CONCLUSIONS
  The addition of sorafenib did not appear to improve the efficacy of treatment when compared with the results expected with standard therapy. A substantial percentage of patients (40%) did not receive any maintenance sorafenib, most often because of early disease progression. The administration of angiogenesis inhibitors concurrently with radiotherapy and temozolomide may optimize the opportunity to improve therapy.
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. jhainsworth@tnonc.com
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Thomas
authors.initials: T
authors.lastname: Ervin
authors.forename: Elke
authors.initials: E
authors.lastname: Friedman
authors.forename: Victor
authors.initials: V
authors.lastname: Priego
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Murphy
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Clark
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Lamar
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage*; D000077157:Sorafenib; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D003606:Dacarbazine; D000077157:Sorafenib; D000077204:Temozolomide