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. Patients and 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. Conclusion: PTK/ZK 1250 mg p.o. once daily is active and well tolerated in patients with imatinib-resistant GIST.
Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate / H. Joensuu, F. De Braud, P. Coco, T. De Pas, C. Putzu, C. Spreafico, P. Bono, S. Bosselli, T. Jalava, D. Laurent, P. Casali. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 19:1(2008 Jan), pp. 173-177.
|Titolo:||Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate|
|Parole Chiave:||gastrointestinal stromal tumor; vatalanib; imatinib; tyrosine kinase inhibitor; targeted therapy; c-kit|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||gen-2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/annonc/mdm419|
|Appare nelle tipologie:||01 - Articolo su periodico|