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帕唑帕尼:治疗晚期肾细胞癌的药物评价。

Pazopanib: a Review in Advanced Renal Cell Carcinoma.

机构信息

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

出版信息

Target Oncol. 2017 Aug;12(4):543-554. doi: 10.1007/s11523-017-0511-8.

Abstract

Pazopanib (Votrient®), an orally administered multi-targeted tyrosine kinase inhibitor that predominantly inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β, and the stem cell factor receptor c-Kit, is approved in the EU, the USA and other countries for the treatment of advanced renal cell carcinoma (RCC). In randomized controlled trials in patients with advanced, predominantly clear-cell RCC, pazopanib significantly improved progression-free survival (PFS) compared with placebo in both treatment-naïve and cytokine-pretreated patients and, as a first-line therapy, was noninferior to intermittent sunitinib with respect to PFS. However, pazopanib had a tolerability profile that was distinguishable from that of sunitinib, based on lower incidences of most adverse events, particularly those associated with discomfort, such as fatigue, hand-foot syndrome and stomatitis. Consistent with this, health-related quality of life (HR-QOL) measures evaluating fatigue, hand/foot soreness and mouth/throat soreness significantly favoured pazopanib over sunitinib. In addition, significantly more patients expressed a preference for pazopanib over sunitinib, primarily because of better overall HR-QOL and less fatigue. Efficacy and tolerability findings from these prospective clinical trials have been substantiated by evidence from a number of retrospective studies evaluating unselected real-world patients with metastatic RCC who received pazopanib (or sunitinib) as a first-line therapy. Thus, data from clinical trials supplemented with that from clinical practice support the use of pazopanib as a standard or alternative first-line treatment for advanced or metastatic RCC.

摘要

帕唑帕尼(Votrient®)是一种口服的多靶点酪氨酸激酶抑制剂,主要抑制血管内皮生长因子受体-1、-2 和-3、血小板衍生生长因子受体-α和-β以及干细胞因子受体 c-Kit,在欧盟、美国和其他国家批准用于治疗晚期肾细胞癌(RCC)。在治疗初治和细胞因子预处理患者的晚期、主要为透明细胞 RCC 的随机对照试验中,与安慰剂相比,帕唑帕尼显著改善了无进展生存期(PFS),作为一线治疗,与间歇性舒尼替尼相比,PFS 非劣效。然而,与舒尼替尼相比,帕唑帕尼的耐受性特征不同,主要是由于大多数不良反应的发生率较低,尤其是与不适相关的不良反应,如疲劳、手足综合征和口腔炎。与此一致,评估疲劳、手足疼痛和口腔/喉咙疼痛的健康相关生活质量(HR-QOL)测量结果明显支持帕唑帕尼优于舒尼替尼。此外,与舒尼替尼相比,更多的患者表示更喜欢帕唑帕尼,主要是因为总体 HR-QOL 更好,疲劳更少。这些前瞻性临床试验的疗效和耐受性发现得到了许多回顾性研究的证据的证实,这些研究评估了接受帕唑帕尼(或舒尼替尼)作为一线治疗的转移性 RCC 未选择的真实世界患者。因此,临床试验数据加上临床实践数据支持将帕唑帕尼作为晚期或转移性 RCC 的标准或替代一线治疗药物。

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