Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane
Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane
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DOI：
10.1200/jco.2007.14.5375
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发表时间：
2008-04-10
影响因子：
45.3
通讯作者：
Miller, Kathy D.
中科院分区：
文献类型：
--
作者：
Burstein, Harold J.;Elias, Anthony D.;Miller, Kathy D.
舒尼替尼是一种口服多靶点酪氨酸激酶抑制剂，可抑制血管内皮生长因子受体（VEGFR）、血小板衍生生长因子受体、干细胞因子受体（KIT）和集落刺激因子-1受体。这第二阶段，开放标签，多中心研究评估舒尼替尼单药治疗转移性乳腺癌（MBC）患者和MethodsSixty-four先前治疗的患者与蒽环类抗生素和紫杉烷接受舒尼替尼50毫克/天，在6周的周期（4周，然后2周关闭治疗）。主要终点为客观缓解率。血浆样本获得药代动力学和生物标志物analysis.ResultsSeven患者实现了部分响应（中位持续时间，19周），给11%的总体响应率。另外3名患者（5%）病情稳定>= 6个月。中位进展时间和总生存期分别为10周和38周。值得注意的是，在三阴性肿瘤和HER 2阳性的曲妥珠单抗治疗患者中发生了缓解。33例患者（52%）在>= 1个周期内需要中断给药，25例患者（39%）需要降低剂量。36例患者（56%）因不良事件（AE）而调整剂量。治疗与血浆VEGF升高以及可溶性VEGF受体和KIT降低相关。最常见的AE为疲乏、恶心、腹泻、粘膜炎症和厌食。大多数不良事件的严重程度为轻度至中度（1级至2级），并有效地管理剂量延迟或reduction.ConclusionSunitinib是积极的，在大量预处理MBC患者。大多数AE的严重程度为轻度至中度，可通过支持性治疗和/或剂量调整进行管理。乳腺癌的进一步研究是必要的。
PurposeSunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor ( KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC).Patients and MethodsSixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis.ResultsSeven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for >= 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during >= 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions.ConclusionSunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.