Division of Neuro-Oncology, Department of Neurological Surgery, University of California, 400 Parnassus Avenue, A-808, San Francisco, CA 94143-0350, USA.
Neuro Oncol. 2010 Aug;12(8):871-81. doi: 10.1093/neuonc/nop054. Epub 2010 Feb 4.
Convection-enhanced delivery (CED) of cintredekin besudotox (CB) was compared with Gliadel wafers (GW) in adult patients with glioblastoma multiforme (GBM) at first recurrence. Patients were randomized 2:1 to receive CB or GW. CB (0.5 microg/mL; total flow rate 0.75 mL/h) was administered over 96 hours via 2-4 intraparenchymal catheters placed after tumor resection. GW (3.85%/7.7 mg carmustine per wafer; maximum 8 wafers) were placed immediately after tumor resection. The primary endpoint was overall survival from the time of randomization. Prestated interim analyses were built into the study design. Secondary and tertiary endpoints were safety and health-related quality-of-life assessments. From March 2004 to December 2005, 296 patients were enrolled at 52 centers. Demographic and baseline characteristics were balanced between the 2 treatment arms. Median survival was 36.4 weeks (9.1 months) for CB and 35.3 weeks (8.8 months) for GW (P = .476). For the efficacy evaluable population, the median survival was 45.3 weeks (11.3 months) for CB and 39.8 weeks (10 months) for GW (P = .310). The adverse-events profile was similar in both arms, except that pulmonary embolism was higher in the CB arm (8% vs 1%, P = .014). This is the first randomized phase III evaluation of an agent administered via CED and the first with an active comparator in GBM patients. There was no survival difference between CB administered via CED and GW. Drug distribution was not assessed and may be crucial for evaluating future CED-based therapeutics.
在胶质母细胞瘤多形性（GBM）首次复发的成年患者中，将 convection-enhanced delivery（CED）的 cintredekin besudotox（CB）与 Gliadel wafers（GW）进行了比较。患者以 2:1 的比例随机接受 CB 或 GW。CB（0.5μg/mL；总流速 0.75mL/h）通过肿瘤切除后放置的 2-4 个脑室内导管在 96 小时内给药。GW（3.85%/7.7mg 卡莫司汀/每片；最大 8 片）在肿瘤切除后立即放置。主要终点是从随机分组时间起的总生存期。研究设计中内置了预先规定的中期分析。次要和三级终点是安全性和健康相关生活质量评估。从 2004 年 3 月至 2005 年 12 月，在 52 个中心招募了 296 名患者。两个治疗组之间的人口统计学和基线特征平衡。CB 的中位生存期为 36.4 周（9.1 个月），GW 为 35.3 周（8.8 个月）（P=0.476）。对于疗效可评估人群，CB 的中位生存期为 45.3 周（11.3 个月），GW 为 39.8 周（10 个月）（P=0.310）。两个治疗组的不良事件谱相似，除了 CB 组的肺栓塞发生率较高（8%比 1%，P=0.014）。这是首次对 CED 给药的药物进行的随机 III 期评估，也是首次在 GBM 患者中进行的活性对照评估。CED 给药的 CB 与 GW 之间无生存差异。未评估药物分布，这对评估未来基于 CED 的治疗方法可能至关重要。
