Virginia Cancer Specialists, INOVA Thoracic Oncology Program, Fairfax, VA 22031, USA.
Clin Lung Cancer. 2012 Jan;13(1):31-8. doi: 10.1016/j.cllc.2011.06.010. Epub 2011 Sep 8.
This open-label phase II study assessed the efficacy and tolerability of eribulin, a non-taxane microtubule dynamics inhibitor with novel mechanism of action, as monotherapy in patients who have advanced non-small-cell lung cancer (NSCLC).
Enrolled patients had progressed during or after platinum-based doublet chemotherapy. Initially, two patient cohorts (taxane-pre-treated and taxane-naïve) received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. To assess tolerability of a second dosing schedule, a cohort of taxane-pre-treated patients received eribulin on days 1 and 8 of a 21-day cycle. The primary endpoint was objective response rate (ORR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by independent radiographic review.
One hundred three patients received eribulin. The ORR was 9.7% (all partial responses [PR]). Overall disease control rate (PR + stable disease) was 55.3%. Median duration of response, progression-free survival, and overall survival were 5.8, 3.4, and 9.4 months, respectively. The most common drug-related adverse events were neutropenia (54%; 49% grade 3/4); fatigue (49%; 11% grade 3, no grade 4); nausea (38%; 1% grade 3, no grade 4); alopecia (32%); anemia (29%, 4% grade 3/4) and neuropathy (23%; 2% grade 3, no grade 4). The 28-day schedule was associated with many dose delays, interruptions, or omissions due to neutropenia (day 15). The 21-day cycle was well-tolerated.
Eribulin monotherapy administered on days 1 and 8 of a 21-day cycle is active and tolerated as second- or later-line chemotherapy for NSCLC.
本开放标签的 II 期研究评估了艾立布林（一种新型作用机制的非紫杉烷微管动力学抑制剂）作为二线或后线化疗药物在晚期非小细胞肺癌（NSCLC）患者中的疗效和耐受性。
入组患者在铂类双联化疗期间或之后进展。最初，两个患者队列（紫杉醇预处理和紫杉醇初治）接受甲磺酸艾立布林（1.4mg/m²），静脉输注 2-5 分钟，每 28 天周期的第 1、8 和 15 天。为了评估第二给药方案的耐受性，一组紫杉醇预处理患者接受每 21 天周期的第 1 和 8 天的艾立布林治疗。主要终点是独立影像学评估采用实体瘤反应评价标准（RECIST）评估的客观缓解率（ORR）。
103 例患者接受了艾立布林治疗。ORR 为 9.7%（均为部分缓解[PR]）。总体疾病控制率（PR+稳定疾病）为 55.3%。中位缓解持续时间、无进展生存期和总生存期分别为 5.8、3.4 和 9.4 个月。最常见的药物相关不良反应是中性粒细胞减少（54%；49%为 3/4 级）；疲劳（49%；11%为 3 级，无 4 级）；恶心（38%；1%为 3 级，无 4 级）；脱发（32%）；贫血（29%，4%为 3/4 级）和周围神经病变（23%；2%为 3 级，无 4 级）。由于中性粒细胞减少（第 15 天），28 天方案导致许多剂量延迟、中断或遗漏。21 天周期耐受性良好。
艾立布林在 21 天周期的第 1 和 8 天给药，作为二线或后线化疗药物，用于 NSCLC 具有活性且耐受良好。
