Phase 2 study of ABT-510 in patients with previously untreated advanced renal cell carcinoma
Phase 2 study of ABT-510 in patients with previously untreated advanced renal cell carcinoma
复制标题
DOI：
10.1158/1078-0432.ccr-07-1477
复制
发表时间：
2007-11-15
影响因子：
11.5
通讯作者：
Figlin, Robert
中科院分区：
文献类型：
--
作者：
Ebbinghaus, Scot;Hussain, Maha;Figlin, Robert
目的：血管生成是肾细胞癌的一个特征。ABT-510是一种血管生成抑制剂，模仿血栓反应蛋白-1的抗血管生成特性。这项研究旨在评估ABT-510在晚期肾细胞癌患者中的安全性和有效性。实验设计：先前未经治疗的转移性或不可切除的肾细胞癌患者随机接受两种剂量的ABT-510中的一种治疗，每天两次自我给药s.c.，在28天的治疗期内，没有中间休息时间。终点为无进展生存期（PFS）、客观缓解率、总生存期和毒性。结果：10 mg 2 d组客观有效率为4%，100 mg 2 d组有2例未确诊pr。中位PFS分别为4.2和3.3个月，6个月PFS分别为39%和32%。中位总生存期为27.8个月（10mg每日两次）和26.1个月（100mg每日两次）。最常见的不良事件是注射部位反应（84%）、疲劳（50%）、头痛（20%）和恶心（19%）。治疗相关的3/4级不良事件发生率较低，包括3次出血发作（胃肠道出血、颅内出血和咯血）和1次血栓形成事件（深静脉血栓形成）。没有死亡归因于ABT-510。结论：ABT-510几乎没有临床活性的证据，进一步评估ABT-510作为治疗晚期肾细胞癌的单一药物是不值得的。有利的安全性的证据可能证明进一步评估联合治疗。
Purpose: Angiogenesis is a characteristic of renal cell carcinoma. ABT-510 is an angiogenesis inhibitor that mimics the antiangiogenic properties of thrombospondin-1. This study was clesigned to assess the safety and efficacy of ABT-510 in patients with advanced renal cell carcinoma. Experimental Design: Patients with previously untreated metastatic or unresectable renal cell carcinoma were randomized to treatment with one of two doses of ABT-510, self-administered s.c. twice daily in 28-day treatment periods without intervening rest periods. End points were progression-free survival (PFS), objective response rate, overall survival, and toxicity. Results: The objective response-rate was 4% in the 10 mg twice daily group, and there were two unconfirmed PRs in the 100 mg twice daily group. Respective median PFS was 4.2 and 3.3 months, with a 6-month PFS of 39% and 32%. Median overall survival was 27.8 months (10 mg twice daily) and 26.1 months (100 mg twice daily). The most frequent adverse events were injection site reactions (84%), fatigue (50%), headache (20%), and nausea (19%). The incidence of treatment-related, grade 3/4 adverse events was low and included three bleeding episodes (gastrointestinal hemorrhage, intracranial hemorrhage, and hemoptysis) and one thrombotic event (deep vein thrombosis). No deaths were attributed to ABT-510. Conclusions: There was little evidence of clinical activity for ABT-510, and further evaluation as a single agent for treating advanced renal cell carcinoma is not warranted. The evidence of a favorable safety profile may justify further evaluation in combination therapy.