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. [10.1093/annonc/mdm419]

Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate

De Braud F;Casali PG
2008-01

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. 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.
gastrointestinal stromal tumor; vatalanib; imatinib; tyrosine kinase inhibitor; targeted therapy; c-kit
Settore MED/06 - Oncologia Medica
ANNALS OF ONCOLOGY
Article (author)
File in questo prodotto:
File Dimensione Formato  
mdm419 (1).pdf

non disponibili

107.3 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/656588
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 62
  • ???jsp.display-item.citation.isi??? 62
social impact