A Phase II Study of Pazopanib in Asian Patients with Recurrent/Metastatic Nasopharyngeal Carcinoma
A Phase II Study of Pazopanib in Asian Patients with Recurrent/Metastatic Nasopharyngeal Carcinoma
复制标题
DOI：
10.1158/1078-0432.ccr-10-3409
复制
发表时间：
2011-08-15
影响因子：
11.5
通讯作者：
Tan, Eng-Huat
中科院分区：
文献类型：
--
作者：
Lim, Wan-Teck;Ng, Quan-Sing;Tan, Eng-Huat
目的：鼻咽癌是亚洲的地方性肿瘤，血管生成对鼻咽癌的生长和进展至关重要。我们假设，帕唑帕尼将有antiangiogenic活性在nasopharyngealcarcinoma.Experimental Design：一个单臂的帕唑帕尼单药治疗研究与WHO II/III型鼻咽癌转移/复发的疾病，至少有一个线的化疗失败的患者。采用Simon最优2阶段设计。东部肿瘤协作组（ECOG）0-2且器官功能良好的患者接受帕唑帕尼800 mg/天治疗，21天为一个周期。主要终点是治疗12周后达到的临床获益率（CR/PR/SD）。次要终点包括毒性和无进展生存期。探索性研究的动态对比增强计算机断层扫描（DCE-CT）配对帕唑帕尼的药代动力学（PK）doneed.Results：33例。患者的ECOG为0-1，中位年龄为50岁（范围36-68岁）。部分缓解2例（6.1%），稳定16例（48.5%），进展11例（33.3%），无效4例（12.1%）。临床获益率为54.5%（95%CI：38.0-70.2）。10例患者（30.3%）接受了超过6个周期（4个月）的治疗，7例（21.2%）PR/SD持续至少6个月。各有1例患者死于鼻出血和心肌梗死。常见的3/4级毒性包括疲乏（15.2%）、手足综合征（15.2%）、厌食（9.1%）、腹泻（6.1%）和呕吐（6.1%）。连续DCE-CT扫描显示肿瘤血流量、渗透性表面积积和血管内血容量分数显着减少。结论：帕唑帕尼在经过深度预治疗的鼻咽癌中显示出令人鼓舞的活性，且毒性可接受。Clin Cancer Res; 17（16）; 5481-9.（C）2011年《非洲标准化评论》。
Purpose: Nasopharyngeal carcinoma is endemic in Asia and angiogenesis is important for growth and progression. We hypothesized that pazopanib would have antiangiogenic activity in nasopharyngeal carcinoma.Experimental Design: A single arm monotherapy study of pazopanib in patients with WHO type II/III nasopharyngeal carcinoma who had metastatic/recurrent disease and failed at least one line of chemotherapy. A Simon's optimal 2-stage design was used. Patients with Eastern Cooperative Oncology Group (ECOG) 0-2 and adequate organ function were treated with pazopanib 800 mg daily on a 21-day cycle. The primary endpoint was clinical benefit rate (CR/PR/SD) achieved after 12 weeks of treatment. Secondary endpoints included toxicity and progression-free survival. Exploratory studies of dynamic-contrast enhanced computed tomography (DCE-CT) paired with pharmacokinetics (PK) of pazopanib was done.Results: Thirty-three patients were accrued. Patients were ECOG 0-1 with median age of 50 years (range 36-68). There were 2 (6.1%) partial responses, 16 (48.5%) stable disease, 11 (33.3%) progressive disease, 4 (12.1%) were not evaluable for response. The clinical benefit rate was 54.5% (95% CI: 38.0-70.2). Ten patients (30.3%) received more than 6 cycles (4 months) of treatment and 7 (21.2%) had PR/SD that lasted at least 6 months. One patient each died from epistaxis and myocardial infarction. Common grade 3/4 toxicities included fatigue (15.2%), hand-foot syndrome (15.2%), anorexia (9.1%), diarrhea (6.1%), and vomiting (6.1%). Serial DCE-CT scans show significant reductions in tumor blood flow, permeability surface area product, and fractional intravascular blood volume.Conclusion: Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile. Clin Cancer Res; 17(16); 5481-9. (C)2011 AACR.