Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade) in chemotherapy-naive patients with advanced stage non-small cell lung cancer (NSCLC)
Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade) in chemotherapy-naive patients with advanced stage non-small cell lung cancer (NSCLC)
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DOI：
10.1016/j.lungcan.2009.05.009
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发表时间：
2010-04-01
期刊：
影响因子：
5.3
通讯作者：
Gucalp, Rasim
中科院分区：
文献类型：
--
作者：
Li, Tianhong;Ho, Liawaty;Gucalp, Rasim
本研究的主要目的是确定硼替佐米作为晚期NSCLC患者一线治疗的客观缓解率。晚期/转移性NSCLC患者具有可测量的疾病，足够的器官功能，ECOG表现状态为0-2，并且之前没有转移性疾病的化疗。患者每21天在第1、4、8和11天静脉滴注硼替佐米1.3 mg/m(2)/天，最多持续8个周期，或直到疾病进展或出现不可接受的毒性。每2个治疗周期后评估肿瘤反应。这项单臂II期研究采用了Simon的两阶段设计。在4家机构招募了14名患者后，该研究在第一阶段终止。未观察到客观反应。3例（21%）病情稳定，分别接受8、6、4周期治疗；稳定期分别为11.5个月、4.2个月和3.4个月。中位进展时间为1.3个月（95% Cl, 0.6-3.0个月）；中位总生存期（OS）为9.9个月（95% Cl, 2.2-27.0个月）。12名患者接受了至少一剂硼替佐米。没有4级毒性或治疗相关死亡。3级毒性包括疲劳（N = 1,8%）、深静脉血栓形成（N = 1,8%）和血小板减少（N = 1,8%）。尽管硼替佐米单药耐受性良好，但在该队列化疗初期转移性非小细胞肺癌中并不活跃。2009爱思唯尔爱尔兰有限公司版权所有。
The primary objective of this study was to determine the objective response rate of bortezomib as a first-line therapy in patients advanced stage NSCLC. Advanced/metastatic NSCLC patients with measurable disease, adequate organ function, ECOG performance status of 0-2, and no prior chemotherapy for metastatic disease were eligible. Patients received intravenously bolus bortezomib 1.3 mg/m(2)/day on days 1, 4, 8 and 11 every 21 days for a maximum of 8 cycles, or until disease progression, or unacceptable toxicity. Tumor response was evaluated after every 2 cycles of therapy. This single-arm phase II study employed the Simon's two-stage design. The study was terminated in the first stage after 14 patients enrolled at 4 institutions. No objective response was observed. Three patients (21%) had stable disease and received 8,6 and 4 cycles of treatment; the duration of stable disease was 11.5, 4.2 and 3.4 months, respectively. Median time to progression was 1.3 months (95% Cl, 0.6-3.0 months); median overall survival (OS) was 9.9 months (95% Cl, 2.2-27.0 months). Twelve patients received at least one dose of bortezomib. There were no grade 4 toxicities or treatment related deaths. Grade 3 toxicities included fatigue (N = 1, 8%), deep vein thrombosis (N = 1,8%) and thrombocytopenia (N = 1, 8%). Although well tolerated, bortezomib monotherapy is not active in this cohort of chemotherapy-naive, metastatic NSCLC. (C) 2009 Elsevier Ireland Ltd. All rights reserved.