Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer
Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer
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DOI：
10.1200/jco.2007.10.8605
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发表时间：
2008-02-01
影响因子：
45.3
通讯作者：
Kris, Mark G.
中科院分区：
文献类型：
--
作者：
Rizvi, Naiyer A.;Riely, Gregory J.;Kris, Mark G.
目的白蛋白结合紫杉醇纳米粒(NAB-Paclitaxel)是一种白蛋白结合的紫杉醇制剂，与紫杉醇相比，在治疗转移性乳腺癌方面显示出更好的疗效。我们进行了这项试验，以确定非小细胞肺癌(NSCLC)患者每周给予NAB-紫杉醇的最大耐受量(MTD)和单药活性。在28天周期的第1、8和15天，患者在30分钟内静脉注射NAB-紫杉醇，而不使用皮质类固醇或抗组胺药物。结果100 mg/m(2)和125 mg/m(2)剂量耐受性良好，无剂量限制性毒性(DLT)。在150 mg/m(2)时，MTD被超过；三名患者中有两名经历了DLT(3级感觉神经病和发热性中性粒细胞减少症)。扩展125 mg/m(2)剂量水平，确定为MTD。40例患者接受125 mg/m(2)剂量的治疗。客观有效率30%(12/40，95%CI，16%~44%)，中位进展时间5个月(95%CI，3~8个月)，中位总生存期11个月(95%CI，7个月未达)。1年生存率为41%。结论NAB-紫杉醇125 mg/m(2)在28天周期的第1、8和15天给药耐受性良好，表现出令人鼓舞的单药活性。未进行激素治疗，也未出现过敏反应。对单药NAB-紫杉醇以及铂类药物组合的额外研究是有必要的。
PurposeNanoparticle albumin-bound paclitaxel ( NAB-paclitaxel) is an albumin-bound formulation of paclitaxel that has demonstrated improved efficacy compared with paclitaxel in the treatment of metastatic breast cancer. We undertook this trial to determine the maximum-tolerated dose ( MTD) and single-agent activity of NAB-paclitaxel administered on a weekly basis to patients with stage IV non-small-cell lung cancer ( NSCLC).Patients and MethodsThis was an open-label, single-arm, phase I/II study. Patients were treated with NAB-paclitaxel intravenously during 30 minutes without corticosteroid or antihistamine premedications on days 1, 8, and 15 of a 28-day cycle. Radiologic tumor assessment was performed every 8 weeks.ResultsDose levels of 100 and 125 mg/m(2) were tolerated without dose-limiting toxicities ( DLTs). At 150 mg/m(2) the MTD was exceeded; two of three patients experienced a DLT ( grade 3 sensory neuropathy and febrile neutropenia). The 125 mg/m(2) dose level was expanded and determined to be the MTD. A total of 40 patients were treated at 125 mg/m(2). The objective response rate was 30% ( 12 of 40 patients; 95% CI, 16% to 44%), median time to progression was 5 months ( 95% CI, 3 to 8 months), and median overall survival was 11 months ( 95% CI, 7 months to not reached). The 1-year survival was 41%.ConclusionNAB-paclitaxel 125 mg/m(2) administered on days 1, 8, and 15 of a 28-day cycle was well tolerated and demonstrated encouraging single-agent activity. No corticosteroid premedication was administered and no hypersensitivity reactions were seen. Additional studies of single-agent NAB-paclitaxel as well as platinum-based combinations are warranted.