title: Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate.
abstract: BACKGROUND
  We evaluated safety and efficacy of PTK787/ZK222584 (PTK/ZK), a novel tyrosine kinase inhibitor of KIT, platelet-derived growth factor receptors and vascular endothelial cell growth factor receptors (VEGFRs), in patients with imatinib-resistant gastrointestinal stromal tumor (GIST). This is the first study of PTK/ZK in this population.
  
  
  METHODS
  Patients with metastatic GIST that had progressed after >/= 4-week treatment with imatinib mesylate were eligible. Prior VEGFR-2 inhibitor therapy was not permitted. PTK/ZK 1250 mg orally once-daily was administered to 15 patients (accrued as a two-stage procedure), most of whom (n = 11) had been unsuccessfully treated with imatinib 800 mg daily, until treatment failure. Patients were monitored at 4- to 8-week intervals.
  
  
  RESULTS
  All 15 patients enrolled were eligible; two (13%) achieved partial response (PR), eight (53%) had stable disease (SD) >/=3 months, and five (33%) progressed. The clinical benefit rate (PR + SD) was 67% (95% CI 38% to 86%). Median time to progression was 8.5 months (range 0.9-24.8+ months). Three patients had not progressed at the time of analysis, including one PR at 24.8 months and two SDs at 16.6 and 18.6 months on treatment. PTK/ZK was generally well tolerated.
  
  
  CONCLUSIONS
  PTK/ZK 1250 mg p.o. once daily is active and well tolerated in patients with imatinib-resistant GIST.
authors: Department of Oncology, University Central Hospital of Helsinki, Helsinki, Finland.
authors: H
authors: H
authors: Joensuu
authors: F
authors: F
authors: De Braud
authors: P
authors: P
authors: Coco
authors: T
authors: T
authors: De Pas
authors: C
authors: C
authors: Putzu
authors: C
authors: C
authors: Spreafico
authors: P
authors: P
authors: Bono
authors: S
authors: S
authors: Bosselli
authors: T
authors: T
authors: Jalava
authors: D
authors: D
authors: Laurent
authors: P G
authors: PG
authors: Casali
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000556:secondary*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010793:Phthalazines / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D016879:Salvage Therapy
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009363:Neoplasm Proteins; D010793:Phthalazines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; C404768:vatalanib; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor