C Dinkic1, M Eichbaum2, M Schmidt3, E M Grischke4, G Gebauer5, H C Fricke6, F Lenz7, M Wallwiener8, F Marme8, A Schneeweiss8, C Sohn8, J Rom8. 1. University of Heidelberg Medical School, Department of Gynecology and Obstetrics, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany. Electronic address: christine.dinkic@med.uni-heidelberg.de. 2. HELIOS Dr. Horst Schmidt Kliniken Wiesbaden, Department of Gynecology and Gynecologic Oncology, Ludwig-Erhard-Str. 100, 65199 Wiesbaden, Germany. 3. University of Mainz Medical School, Department of Gynecology and Obstetrics, Langenbeckstr. 1, 55131 Mainz, Germany. 4. University of Tuebingen Medical School, Department of Gynecology and Obstetrics, Calwerstraße 7, 72076 Tuebingen, Germany. 5. Klinik für Gynäkologie und gynäkologische Onkologie, Marienkrankenhaus Hamburg, Alfredstraße 9, 22087 Hamburg, Germany. 6. Frauenklinik Klinikum Konstanz, Luisenstraße 7, 78464 Konstanz, Germany. 7. Frauenklinik Sankt-Marienkrankenhaus Ludwigshafen, Salzburger Straße 15, 67067 Ludwigshafen, Germany. 8. University of Heidelberg Medical School, Department of Gynecology and Obstetrics, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
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, 50mg cyclophosphamide were combined with 400 to 800mg pazopanib daily. RESULTS: Sixteen patients were treated; mean age was 66years. 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 600mg pazopanib daily. Median number of administered cycles was 6 (2-13), with three patients being treated for at least 13months. Median progression-free survival (PFS) and overall survival (OS) were 8.35months and 24.95months, 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 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. TRIAL REGISTRATION: Clin.trial.gov registry no.: NCT01238770.
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, 50mg cyclophosphamide were combined with 400 to 800mg pazopanib daily. RESULTS: Sixteen patients were treated; mean age was 66years. 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 600mg pazopanib daily. Median number of administered cycles was 6 (2-13), with three patients being treated for at least 13months. Median progression-free survival (PFS) and overall survival (OS) were 8.35months and 24.95months, 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 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. TRIAL REGISTRATION: Clin.trial.gov registry no.: NCT01238770.