title: Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A retrospective analysis.
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKI) improve the outcome of patients with advanced gastrointestinal stromal tumour (GIST), but treatment failure is frequent, and prognosis then bleak. Smaller trials in this setting suggested activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and RAF serine/threonine kinases.
  
  
  METHODS
  We retrospectively evaluated the efficacy of sorafenib, starting dose 400mg twice daily, in a large community-based cohort of 124 patients treated in 12 European and one United States (U.S.) cancer centre. All but one patient had a WHO performance score 0-2. All had failed both imatinib and sunitinib, 68 patients nilotinib and 26 had failed investigational therapy, too.
  
  
  RESULTS
  Twelve (10%) patients responded to sorafenib and 70 (57%) patients achieved disease stabilisation. Sorafenib was moderately tolerated, and toxicity reported in 56% of the patients. Rash, hand-foot-syndrome and diarrhea occurred frequently. Sorafenib dosage was reduced in a third of patients, but this did not have an impact on progression-free survival (PFS) (p=0.15). Median PFS was 6.4 months (95% confidence interval [CI], 4.6-8.0 months) and median overall survival (OS) 13.5 months (95% CI, 10.0-21.0 months). Patients with a good performance status and those who responded to sorafenib had a significant better PFS.
  
  
  CONCLUSIONS
  We conclude that sorafenib is active in GIST resistant to imatinib, sunitinib and nilotinib. These results warrant further investigation of sorafenib or similar molecules in GIST.
authors.affiliation: Centre Pluridisciplinaire d' Oncologie, University Hospital Lausanne, Lausanne, Switzerland. michael.montemurro@usz.ch
authors.forename: M
authors.initials: M
authors.lastname: Montemurro
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.forename: U
authors.initials: U
authors.lastname: Bitz
authors.forename: J
authors.initials: J
authors.lastname: Schütte
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
authors.forename: H
authors.initials: H
authors.lastname: Joensuu
authors.forename: J
authors.initials: J
authors.lastname: Trent
authors.forename: S
authors.initials: S
authors.lastname: Bauer
authors.forename: P
authors.initials: P
authors.lastname: Rutkowski
authors.forename: F
authors.initials: F
authors.lastname: Duffaud
authors.forename: D
authors.initials: D
authors.lastname: Pink
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; 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*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D016879:Salvage Therapy; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D007211:Indoles; D010671:Phenylurea Compounds; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D009536:Niacinamide; D000068877:Imatinib Mesylate; D000077157:Sorafenib; C498826:nilotinib; D000077210:Sunitinib