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.

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.

• Authors: H Joensuu, F De Braud, P Coco, T De Pas, C Putzu, C Spreafico, P Bono, S Bosselli, T Jalava, D Laurent, P G Casali
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 19 Issue 1 Pg. 173-7 (Jan 2008) ISSN: 1569-8041 [Electronic] England
• PMID: 17698976 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzamides
• Neoplasm Proteins
• Phthalazines
• Piperazines
• Protein Kinase Inhibitors
• Pyridines
• Pyrimidines
• vatalanib
• Imatinib Mesylate
• Proto-Oncogene Proteins c-kit
• Receptor Protein-Tyrosine Kinases
• Receptors, Platelet-Derived Growth Factor
• Receptors, Vascular Endothelial Growth Factor

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Benzamides
• Disease Progression
• Drug Resistance, Neoplasm
• Female
• Gastrointestinal Neoplasms (drug therapy, pathology)
• Gastrointestinal Stromal Tumors (drug therapy, secondary)
• Humans
• Imatinib Mesylate
• Male
• Middle Aged
• Neoplasm Proteins (antagonists & inhibitors)
• Phthalazines (therapeutic use)
• Piperazines (pharmacology, therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins c-kit (drug effects)
• Pyridines (therapeutic use)
• Pyrimidines (pharmacology, therapeutic use)
• Receptor Protein-Tyrosine Kinases (antagonists & inhibitors)
• Receptors, Platelet-Derived Growth Factor (antagonists & inhibitors)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)
• Salvage Therapy