Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 5042
© 2005 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schroder, W. Articles by Du Bois, A. Search for Related Content PubMed Articles by Schroder, W. Articles by Du Bois, A.

Abstract

A phase IB, open label, safety and pharmacokinetic (PK) study of escalating doses of PTK787/ZK 222584 in combination with paclitaxel and carboplatin in patients (PTs) with stage IIC to IV epithelial ovarian cancer

Zentralkrankenhaus/Frauenklinik, Bremen, Germany; UMC Utrecht, Utrecht, The Netherlands; Ctr Paul Papin, Angers, France; Ctr Rene Gauducheau, Nantes, France; Inst Paoli Calmettes, Marseilles, France; Schering AG, Berlin, Germany; Novartis Pharm Corp., East Hanover, NJ; Dr. Horst Schmidt Klin, Wiesbaden, Germany

5042

Background: PTK787/ZK 222584 (PTK/ZK) is a novel, oral, small molecule, anti-angiogenisis compound that blocks tyrosine kinase signaling from all known vascular endothelial growth factor VEGF receptors (VEGF-Rs). Based on its biologic activity, PTK/ZK is under investigation for the treatment of Pts with solid tumors known to overexpress VEGF-R such as ovarian cancer. Methods: An open label, multicenter, phase IB dose escalation study was initiated to evaluate PTK/ZK in combination with chemotherapy as first line therapy in Pts with stage IIC to IV epithelial ovarian cancer. Treatment consisted of paclitaxel administered as a 3-hour infusion on day 1 of each 21-day cycle at a dose of 175 mg/m² following appropriate premedication. Carboplatin was given immediately after paclitaxel as a 30-min IV infusion to a target area under the plasma concentration time curve (AUC) of 5 mg min/mL. PTK/ZK was given once daily from day 3 to day 21 of each chemotherapy cycle. PTK/ZK was withheld on the day of chemotherapy and the day following chemotherapy. Cohorts of 3 to 6 Pts received doses of PTK/ZK at 250 mg, 500 mg, 750 mg, 1000 mg or 1250 mg/day. Goals of this study were to determine the maximal tolerated dose (MTD) of PTK/ZK, dose limiting toxicity (DLT) of PTK/ZK and to characterize the PK of PTK/ZK with carboplatin and paclitaxel. Results: 18 Pts were evaluated to date, with 16 evaluable for DLT, (n=3, 4, 3, 3, 3 from the 250 mg, 500 mg, 750 mg, 1000 mg and 1250 mg cohorts respectively). 14 patients were evaluable for PK (n=3, 3, 3, 2, 3 from the 250 mg, 500 mg, 750 mg, 1000 mg and 1250 mg cohorts respectively.) No DLTs or PTK related serious adverse events (AEs) were reported. None of the Pts discontinued the study due to AEs. Grade 1 and 2 hypertension was the most frequently reported AE. PTK/ZK plasma level was not affected by paclitaxel or carboplatin. PTK/ZK also has no impact on the systemic exposure of carboplatin. The effect of PTK/ZK at the 1250 mg dose on paclitaxel and its metabolites require further study. Conclusion: Combination of PTK/ZK with paclitaxel and carboplatin is feasible and shows acceptable safety profile.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Schering AG

Abstract presentation from the 2005 ASCO Annual Meeting