title: Vatalanib for metastatic gastrointestinal stromal tumour (GIST) resistant to imatinib: final results of a phase II study.
abstract: BACKGROUND
  Vatalanib (PTK787/ZK 222584) inhibits a few tyrosine kinases including KIT, platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs). We report efficacy and safety results of vatalanib in advanced gastrointestinal stromal tumour (GIST) resistant to imatinib or both imatinib and sunitinib.
  
  
  METHODS
  Forty-five patients whose metastatic GIST had progressed on imatinib were enrolled. Nineteen (42.2%) patients had received also prior sunitinib. Vatalanib 1250 mg was administered orally daily.
  
  
  RESULTS
  Eighteen patients (40.0%; 95% confidence interval (CI), 25.7-54.3%) had clinical benefit including 2 (4.4%) confirmed partial remissions (PR; duration, 9.6 and 39.4 months) and 16 (35.6%) stabilised diseases (SDs; median duration, 12.5 months; range, 6.0-35.6+ months). Twelve (46.2%) out of the 26 patients who had received prior imatinib only achieved either PR or SD compared with 6 (31.6%, all SDs) out of the 19 patients who had received prior imatinib and sunitinib (P=0.324). The median time to progression was 5.8 months (95% CI, 2.9-9.5 months) in the subset without prior sunitinib and 3.2 (95% CI, 2.1-6.0) months among those with prior imatinib and sunitinib (P=0.992). Vatalanib was generally well tolerated.
  
  
  CONCLUSIONS
  Vatalanib is active despite its narrow kinome interaction spectrum in patients diagnosed with imatinib-resistant GIST or with imatinib and sunitinib-resistant GIST.
authors.affiliation: Department of Oncology, University Central Hospital of Helsinki, Haartmaninkatu 4, Helsinki FIN-00029, Finland. heikki.joensuu@hus.fi
authors.forename: H
authors.initials: H
authors.lastname: Joensuu
authors.forename: F
authors.initials: F
authors.lastname: De Braud
authors.forename: G
authors.initials: G
authors.lastname: Grignagni
authors.forename: T
authors.initials: T
authors.lastname: De Pas
authors.forename: G
authors.initials: G
authors.lastname: Spitalieri
authors.forename: P
authors.initials: P
authors.lastname: Coco
authors.forename: C
authors.initials: C
authors.lastname: Spreafico
authors.forename: S
authors.initials: S
authors.lastname: Boselli
authors.forename: F
authors.initials: F
authors.lastname: Toffalorio
authors.forename: P
authors.initials: P
authors.lastname: Bono
authors.forename: T
authors.initials: T
authors.lastname: Jalava
authors.forename: C
authors.initials: C
authors.lastname: Kappeler
authors.forename: M
authors.initials: M
authors.lastname: Aglietta
authors.forename: D
authors.initials: D
authors.lastname: Laurent
authors.forename: P G
authors.initials: PG
authors.lastname: Casali
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010793:Phthalazines / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010793:Phthalazines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; C404768:vatalanib; D000068877:Imatinib Mesylate; D000077210:Sunitinib