Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer

• Verfasst von: Dinkic, Christine [VerfasserIn]
• Verfasst von: Wallwiener, Markus [VerfasserIn]
• Verfasst von: Marmé, Frederik [VerfasserIn]
• Verfasst von: Schneeweiss, Andreas [VerfasserIn]
• Verfasst von: Sohn, Christof [VerfasserIn]
• Verfasst von: Rom, Joachim [VerfasserIn]
• Titel: Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer
• Titelzusatz: results of the PACOVAR-trial
• Verf.angabe: C. Dinkic, M. Eichbaum, M. Schmidt, E.M. Grischke, G. Gebauer, H.C. Fricke, F. Lenz, M. Wallwiener, F. Marme, A. Schneeweiss, C. Sohn, J. Rom
• Umfang: 6 S.
• Fussnoten: Gesehen am 10.04.2018
• Titel Quelle: Enthalten in: Gynecologic oncology
• Jahr Quelle: 2017
• Band/Heft Quelle: 146(2017), 2, S. 279-284
• ISSN Quelle: 1095-6859
• DOI: doi:10.1016/j.ygyno.2017.05.013
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1571879617

Abstract

Purpose. The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. Patients and methods. This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously treated ovarian, peritoneal, or fallopian tube cancer. Here, 50 mg cyclophosphamide were combined with 400 to 800 mg pazopanib daily. Results. Sixteen patients were treated; mean age was 66 years. At dose levels (DL) I and II, one instance of dose-limiting toxicity (DLT) was seen in one of 6 patients. At DL III, two of four patients showed a DLT, leading to a maximum tolerated dose (MTD) of 600 mg pazopanib daily. Median number of administered cycles was 6 (2−13), with three patients being treated for at least 13 months. Median progression-free survival (PFS) and overall survival (OS) were 8.35 months and 24.95 months, respectively. 155 adverse events (AE) occurred, most frequently elevation of liver enzymes, leukopenia, diarrhea and fatigue. Altogether, five serious adverse events (SAE) developed in four patients. Conclusion. Pazopanib 600 mg daily p.o. and metronomic cyclophosphamide 50 mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population.