Pazopanib, a Multikinase Angiogenesis Inhibitor, in Patients With Relapsed or Refractory Advanced Soft Tissue Sarcoma: A Phase II Study From the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC Study 62043)
Pazopanib, a Multikinase Angiogenesis Inhibitor, in Patients With Relapsed or Refractory Advanced Soft Tissue Sarcoma: A Phase II Study From the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC Study 62043)
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DOI：
10.1200/jco.2008.21.3223
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发表时间：
2009-07-01
影响因子：
45.3
通讯作者：
Blay, Jean-Yves
中科院分区：
文献类型：
--
作者：
Sleijfer, Stefan;Ray-Coquard, Isabelle;Blay, Jean-Yves
PurposeGiven the importance of angiogenesis in soft tissue sarcoma（STS），pazopanib，a oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor，was explored in patients with advanced STS.Patients and MethodsPatients with intermediate-or high-grade advanced STS who were included for chemotherapy or who had not received more than two prior cytotoxic agents for advanced disease，有记录的进展，有足够的性能状态，并有良好的器官功能的人是合格的。每日给予帕唑帕尼800 mg。主要终点是12周时的无进展率（PFR 12周）。次要终点是反应、安全性和总生存期。研究了四种不同的分层：脂肪细胞STS、平滑肌肉瘤、滑膜肉瘤和其他STS类型。A Simon两阶段设计（P1 = 40%; P0 = 20%; α = β = .1）为每个strature.Results142例患者入组。脂肪细胞STS层在第一阶段后闭合，活动不足（PFR 12周，5/19 [26%]）。PFR 12周在平滑肌肉瘤队列中的41例患者中为18例（44%），在滑膜肉瘤中的37例患者中为18例（49%），在其他STS类型中的41例患者中为16例（39%）。与接受二线化疗的历史对照组相比，达到主要终点的三个队列的无进展生存期和总生存期延长。最常见的药物相关毒性为高血压、疲乏、色素减退和恶心。其他毒性包括肝酶升高、骨髓抑制和蛋白尿，所有毒性大多为1 - 2级。最常见的3至4级毒性是高胆红素血症（6.3%），高血压（7.7%），疲劳（7.7%）。Conclusionpazopanib是耐受性良好的患者复发，先进的STS和表现出有趣的活动，值得进一步研究平滑肌肉瘤，滑膜肉瘤，和其他STS类型的患者。
PurposeGiven the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS.Patients and MethodsPatients with intermediate-or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR 12 weeks). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = beta = .1) for each stratum.ResultsOne hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR12 weeks, five [26%] of 19). PFR12 weeks was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%).ConclusionPazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.