University of Heidelberg Medical School, Department of Gynecology and Obstetrics, Voss-Str, 9, 69115 Heidelberg, Germany.
BMC Cancer. 2011 Oct 20;11:453. doi: 10.1186/1471-2407-11-453.
The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC.
METHODS/DESIGN: This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I) as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II). The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I) and the overall response rate according to RECIST criteria (phase II). Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject).
The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer.
复发性铂耐药上皮性卵巢癌（EOC）患者的预后较差，目前尚无标准治疗方法。新出现的证据表明，抗血管生成治疗方法在 EOC 中具有重要作用，特别是与低剂量化疗的节拍式应用联合使用。新型研究性口服抗血管生成药物帕唑帕尼（pazopanib）靶向血管内皮生长因子受体（VEGFR）、血小板衍生生长因子受体（PDGFR）和 c-kit，目前正在不同肿瘤类型中进行研究，并且已经在复发性肾细胞癌中作为一线治疗药物使用。帕唑帕尼联合节拍式口服环磷酰胺的联合治疗可能为复发性铂耐药 EOC 患者提供一种耐受良好的治疗选择。
方法/设计：本研究设计为一项多中心 I/II 期试验，旨在评估帕唑帕尼的最佳剂量（I 期），以及帕唑帕尼联合节拍式环磷酰胺治疗复发性铂耐药、预处理卵巢癌患者的姑息治疗中的活性和耐受性（II 期）。患者人群包括组织学或细胞学证实的 EOC、输卵管癌或腹膜癌患者，这些癌症对铂类耐药或难治。患者必须根据 RECIST 标准有可测量的疾病，并且必须已经接受了现有标准化疗的治疗。主要目标是确定帕唑帕尼的最佳剂量（I 期）和根据 RECIST 标准的总缓解率（II 期）。次要目标是疾病进展时间、总生存期、安全性和耐受性。治疗持续时间为疾病进展或研究药物方案不耐受（每个受试者最多 13 个周期，最长 52 周）。
目前的 I/II 期试验将阐明多靶点抗血管生成酪氨酸激酶抑制剂 GW 786034（pazopanib）联合口服环磷酰胺作为复发性预处理卵巢癌患者挽救治疗的潜力。
