Annals of Oncology Advance Access originally published online on August 14, 2007
Annals of Oncology 2008 19(1):173-177; doi:10.1093/annonc/mdm419
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sarcomas |
Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate
1 Department of Oncology, University Central Hospital of Helsinki, Helsinki, Finland
2 Department of Oncology, European Institute of Oncology, Milano, Italy
3 Bayer Schering Pharma AG, Berlin, Germany
4 Adult Sarcoma Medical Oncology Unit, Istituto Nazionale Tumori, Milano, Italy
* Correspondence to: Dr H. Joensuu, Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00029 Helsinki, Finland. Tel: +358-9-471 73208; Fax: +358-9-471 74202; E-mail: heikki.joensuu{at}hus.fi
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.
Key words: gastrointestinal stromal tumor, vatalanib, imatinib, tyrosine kinase inhibitor, targeted therapy, c-kit
Received for publication February 1, 2007. Accepted for publication July 19, 2007.
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