Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Clin Cancer Res. 2010 Mar 1;16(5):1634-41. doi: 10.1158/1078-0432.CCR-09-0379. Epub 2010 Feb 23.
Ixabepilone (Ixempra; BMS-247550) is an epothilone B analog and nontaxane microtubule-stabilizing compound with clinical activity in a range of solid tumors. This phase II study was conducted to assess the efficacy and safety of ixabepilone in patients with metastatic renal cell carcinoma.
Patients with metastatic renal cell carcinoma who had measurable disease and had not received previous cytotoxic or targeted therapy were treated with 6 mg/m(2) ixabepilone i.v. daily for 5 days every 3 weeks. Levels of Glu-terminated and acetylated tubulin, markers of microtubule stabilization, were assessed by Western blot. VHL gene mutation status was determined by sequencing.
Eighty-seven patients received a total of 590 cycles, with a median of 5 cycles (range, 1-29). The overall response rate was 13% (Response Evaluation Criteria in Solid Tumor). One patient had a complete response, 10 patients had partial responses, and 59 patients had stable disease. The median duration of response was 5.5 months. The median overall survival of renal cell carcinoma Motzer grade 0 and 1 patients with clear cell histology was 19.25 months. Treatment-related adverse events were primarily alopecia, gastrointestinal toxicity, neuropathy, and fatigue. Biopsies were done at baseline and after five doses of ixabepilone. Microtubule target engagement was achieved in 84.6% to 92.3% of patients evaluated. No correlation was identified between the target engagement, VHL gene mutation status, and clinical response.
Ixabepilone can cause tumor regression in some patients with metastatic renal cell carcinoma and could be considered in combination regimens with other therapies.
伊沙匹隆（Ixempra；BMS-247550）是一种埃坡霉素 B 类似物和非紫杉烷类微管稳定剂化合物，在多种实体肿瘤中具有临床活性。这项 II 期研究旨在评估伊沙匹隆在转移性肾细胞癌患者中的疗效和安全性。
患有转移性肾细胞癌且有可测量疾病且未接受过细胞毒性或靶向治疗的患者，接受 6mg/m²伊沙匹隆静脉滴注，每天一次，连用 5 天，每 3 周一次。通过 Western blot 评估 Glu 末端和乙酰化微管蛋白的水平，作为微管稳定的标志物。通过测序确定 VHL 基因突变状态。
87 名患者共接受了 590 个周期的治疗，中位数为 5 个周期（范围 1-29）。总体缓解率为 13%（实体瘤反应评估标准）。1 例患者完全缓解，10 例患者部分缓解，59 例患者病情稳定。缓解持续时间的中位数为 5.5 个月。具有透明细胞组织学的肾细胞癌 Motzer 分级 0 和 1 患者的中位总生存期为 19.25 个月。治疗相关不良事件主要为脱发、胃肠道毒性、周围神经病变和疲劳。在基线和伊沙匹隆治疗 5 个剂量后进行了活检。在评估的 84.6%至 92.3%的患者中达到了微管靶标结合。未发现靶标结合、VHL 基因突变状态和临床反应之间存在相关性。
伊沙匹隆可使部分转移性肾细胞癌患者的肿瘤消退，可考虑与其他治疗联合应用。
