Okuma Yusuke, Hosomi Yukio, Takahashi Satoshi, Nakahara Yoshiro, Watanabe Kageaki, Nagamata Makoto, Takagi Yusuke, Mikura Shinichiro
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Honkomagome 3-18-22, Bunkyo, Tokyo, 113-8677, Japan.
Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Minato, Tokyo, 105-8461, Japan.
Cancer Chemother Pharmacol. 2016 Aug;78(2):383-8. doi: 10.1007/s00280-016-3092-9. Epub 2016 Jun 23.
The objective of this clinical trial was to explore the efficacy and tolerability of first-line chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a novel agent that uses a drug delivery system, plus carboplatin, in elderly Japanese patients with advanced non-small cell lung cancer (NSCLC).
In this phase II, single-arm, open-label, single-institutional study, we aimed to enroll 37 elderly patients, aged more than 70 years, with advanced NSCLC of performance status 0 or 1. The patients received each cycle of first-line therapy consisting of 100 mg/m(2) nab-paclitaxel intravenously administered on days 1, 8, and 15 of each 21-day cycle, plus carboplatin area under curve 6 on day 1 of each 21-day cycle, for up to six cycles. The primary end point was determining the objective response rate, and secondary endpoints were progression-free survival, overall survival, and safety.
The study was interrupted early because of two treatment-related deaths and 1 life-threatening severe adverse event; therefore, only 10 patients (median age, 77 years; range 71-82 years) were enrolled. The primary end point of the objective response was 50 % for the 10 patients analyzed. Progression-free survival was 4.48 months [95 % confidence interval (CI) 0.36-6.44], and overall survival was 7.89 months (95 % CI 0.36-26.88). Common treatment-related adverse events higher than grade 2 included decreased neutrophil counts, anemia, decreased albumin, anorexia, and peripheral neuropathy. Regarding severe adverse events, two patients had febrile neutropenia and lung infection. Two patients died, and one patient had febrile neutropenia with intubation during the first cycle. The Data and Safety Monitoring Committee therefore recommended interruption of patient enrollment.
Nab-paclitaxel plus carboplatin, without dose reduction, is indicated to be toxic and intolerable as first-line chemotherapy in elderly Japanese patients with advanced NSCLC. Care must be taken when extrapolating the results of a clinical trial into clinical practice, particularly when the resulting subgroup analysis is of elderly patients because this patient group is composed of a heterogeneous population.
UMIN-CTR identifier: UMIN000010738.
本临床试验的目的是探讨一线化疗使用纳米白蛋白结合型紫杉醇（nab-紫杉醇）加卡铂对老年日本晚期非小细胞肺癌（NSCLC）患者的疗效和耐受性，nab-紫杉醇是一种采用药物递送系统的新型药物。
在这项II期单臂、开放标签、单机构研究中，我们旨在招募37名70岁以上、体能状态为0或1的晚期NSCLC老年患者。患者接受每21天为一个周期的一线治疗，每个周期的第1、8和15天静脉注射100mg/m² nab-紫杉醇，每个21天周期的第1天静脉注射曲线下面积为6的卡铂，最多进行六个周期。主要终点是确定客观缓解率，次要终点是无进展生存期、总生存期和安全性。
由于两例与治疗相关的死亡和1例危及生命的严重不良事件，研究提前中断；因此，仅招募了10名患者（中位年龄77岁；范围71 - 82岁）。对这10名患者分析的客观缓解主要终点为50%。无进展生存期为4.48个月[95%置信区间（CI）0.36 - 6.44]，总生存期为7.89个月（95%CI 0.36 - 26.88）。高于2级的常见治疗相关不良事件包括中性粒细胞计数减少、贫血、白蛋白降低、厌食和周围神经病变。关于严重不良事件，两名患者出现发热性中性粒细胞减少和肺部感染。两名患者死亡，一名患者在第一个周期出现发热性中性粒细胞减少并插管。因此，数据与安全监测委员会建议中断患者入组。
nab-紫杉醇加卡铂，不减量，对老年日本晚期NSCLC患者作为一线化疗显示出毒性且耐受性差。将临床试验结果外推至临床实践时必须谨慎，尤其是当由此产生的亚组分析是针对老年患者时，因为该患者群体由异质性人群组成。
UMIN-CTR标识符：UMIN000010738
