Article
Anti-angiogenesis Treatment with PTK/ZK in Ovarian Cancer: A Phase IB, Open Label, Safety and Pharmacokinetics (PK) Study of Escalating Doses of PTK787/ZK 222584 (PTK/ZK) in Combination With Paclitaxel and Carboplatin in Patients (pts) With Stage IC to IV Epithelial Ovarian Cancer
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Published: | March 20, 2006 |
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Background: Vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs) are important mediators of tumor growth and metastasis and their expression is associated with poor prognosis in epithelial ovarian cancer. PTK/ZK is a novel, oral, angiogenesis and lymphangiogenesis inhibitor that blocks tyrosine kinase signaling from all known VEGFRs.
Methods: An open-label, multicenter, phase-IB, dose-escalation study evaluated PTK/ZK with chemotherapy as first line-therapy in pts with stage IC-IV epithelial ovarian cancer. Paclitaxel was administered as a 3-hour infusion on day 1 of each 21-day cycle at 175 mg/m2. Carboplatin was given immediately after paclitaxel as a 30-min IV infusion to an AUC of 5 mg min/mL. PTK/ZK was given daily from day 3-21 of each cycle. Cohorts of 3 to 6 pts received doses of PTK/ZK at 250, 500, 750, 1,000 or 1,250 mg/day. MTD and DLT of PTK/ZK were assessed; PK of PTK/ZK, carboplatin and paclitaxel was characterized.
Results: 19 pts were evaluated; 16 for DLT; 18 for PK. No DLTs or PTK/ZK-related SAEs were reported. One pt discontinued due to AEs. Grade 1-2 hypertension was the most common AE. Steady-state PTK/ZK plasma levels were constant between cycle 1-2. PTK/ZK has no impact on systemic exposure of free platinum. Paclitaxel exposure was not affected at the biologically active dose of 1,250 mg/day PTK/ZK. Additional data are being collected at the 1,250 mg dose level.
Conclusion: PTK/ZK with paclitaxel and carboplatin is feasible and shows acceptable safety. Updated data will be presented.