Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
Clin Cancer Res. 2011 Aug 15;17(16):5481-9. doi: 10.1158/1078-0432.CCR-10-3409. Epub 2011 Jun 28.
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.
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.
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.
Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile.
鼻咽癌在亚洲地区高发，血管生成对于肿瘤的生长和进展非常重要。我们推测帕唑帕尼在鼻咽癌中具有抗血管生成活性。
这是一项在患有 II/III 型世界卫生组织（WHO）分类的鼻咽癌、且转移性/复发性疾病经至少一线化疗失败的患者中开展的帕唑帕尼单药治疗、开放性、单臂研究。采用西蒙二阶段最优设计。ECOG 评分为 0-2 且器官功能充足的患者接受帕唑帕尼 800mg 每日治疗，21 天为一个周期。主要终点为治疗 12 周后的临床获益率（CR/PR/SD）。次要终点包括毒性和无进展生存期。还进行了动态对比增强 CT（DCE-CT）与帕唑帕尼药代动力学（PK）的配对探索性研究。
共入组 33 例患者。患者的 ECOG 评分为 0-1，中位年龄为 50 岁（范围 36-68 岁）。2 例（6.1%）患者部分缓解，16 例（48.5%）患者疾病稳定，11 例（33.3%）患者疾病进展，4 例（12.1%）患者无法评估疗效。临床获益率为 54.5%（95%CI：38.0-70.2）。10 例（30.3%）患者接受了超过 6 个周期（4 个月）的治疗，7 例（21.2%）患者的缓解持续时间至少为 6 个月。各有 1 例患者因鼻出血和心肌梗死死亡。常见的 3/4 级毒性包括疲劳（15.2%）、手足综合征（15.2%）、厌食（9.1%）、腹泻（6.1%）和呕吐（6.1%）。连续的 DCE-CT 扫描显示肿瘤血流、通透性表面积产品和血管内血容量分数显著降低。
帕唑帕尼在经大量预处理的鼻咽癌患者中显示出令人鼓舞的疗效，且毒性谱可接受。
