title: Sorafenib plus daily low-dose temozolomide for relapsed glioblastoma: a phase II study.
abstract: BACKGROUND
  Bevacizumab has provided encouraging results in relapsed glioblastoma multiforme (GBM). Pre-clinical and clinical investigations also showed that continuous low-dose temozolomide has some antiangiogenic activity. Based on this evidence, a phase II trial was designed to investigate an oral regimen of sorafenib, an oral multikinase inhibitor, and metronomic temozolomide for relapsed GBM.
  
  
  METHODS
  Forty-three patients (median age=60.0 years) naive for antiangiogenic agents received 400 mg sorafenib twice daily plus TMZ 40 mg/m(2)/day until disease progression.
  
  
  RESULTS
  Toxicity, mostly grade 1-2, was manageable. Grade 3-4 toxicities were hand-foot syndrome (n=4), hypertension (n=2), and fatigue (n=3). Five patients (12%) achieved partial response, 18 (43%) stable disease, 20 (48%) showed progression. The median time-to-progression was 3.2 months, 6-month progression-free survival was 26%, and median overall survival was 7.4 months.
  
  
  CONCLUSIONS
  This combination of sorafenib and temozolomide was feasible and safe, showing some activity in patients with relapsed GBM.
authors.affiliation: Istituto Oncologico Veneto-IRCCS, Medical Oncology 1 - Via Gattamelata, 64, 35128 Padova, Italy. fable.zustovich@ioveneto.it
authors.forename: Fable
authors.initials: F
authors.lastname: Zustovich
authors.forename: Lorenza
authors.initials: L
authors.lastname: Landi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardi
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Luca
authors.initials: L
authors.lastname: Galli
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.forename: Domenico
authors.initials: D
authors.lastname: Amoroso
authors.forename: Costanza
authors.initials: C
authors.lastname: Galli
authors.forename: Michele
authors.initials: M
authors.lastname: Andreuccetti
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D000077157:Sorafenib; D016019:Survival Analysis; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D003606:Dacarbazine; D000077157:Sorafenib; D000077204:Temozolomide
keywords: Chemotherapy; glioblastoma; relapse; sorafenib; temozolomide