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Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

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.

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Cat.No. Product Name Information Publications Customer Product Validation
S1035 Pazopanib HCl (GW786034 HCl) Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces autophagic Type II cell death. (42) (3)

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