Groves Morris D, Puduvalli Vinay K, Chang Susan M, Conrad Charles A, Gilbert Mark R, Tremont-Lukats Ivo W, Liu Ta-Jen, Peterson Pamela, Schiff David, Cloughesy Timothy F, Wen Patrick Y, Greenberg Harry, Abrey Lauren E, DeAngelis Lisa M, Hess Kenneth R, Lamborn Kathleen R, Prados Michael D, Yung W K Alfred
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1400 Holcombe, 431, Houston, TX, 77030, USA.
J Neurooncol. 2007 Feb;81(3):271-7. doi: 10.1007/s11060-006-9225-y. Epub 2006 Sep 22.
Laboratory and clinical data suggest that the anti-angiogenic agent, thalidomide, if combined with cytotoxic agents, may be effective against recurrent glioblastoma multiforme (GBM).
To determine 6-month progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in adults with recurrent GBM.
Eligible patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was given at 150-200 mg/m(2)/day on days 1-5 of each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime (days 1-28) and increased to 1,200 mg as tolerated. Patients were evaluated with magnetic resonance imaging scans every 56 days. The study was designed to detect an increase of the historical 6PFS for GBM from 10 to 30%.
Forty-four patients were enrolled, 43 were evaluable for efficacy and safety. The study population included 15 women, 29 men; median age was 53 years (range 32-84); median Karnofsky performance status was 80% (range 60-100%). Thirty-six (82%) patients were chemotherapy-naïve. There were 57 reports of toxicity of grade 3 or greater. Non-fatal grade 3-4 granulocytopenia occurred in 15 patients (34%). The objective response rate was 7%. The estimated probability of being progression-free at 6 months with this therapy is 24% [95% confidence interval (C.I.) 12-38%]. The median time to progression is 15 weeks (95% C.I. 10-20 weeks). There was no observed correlation between serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and the 6PFS outcome.
This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.
实验室和临床数据表明，抗血管生成药物沙利度胺若与细胞毒性药物联合使用，可能对复发性多形性胶质母细胞瘤（GBM）有效。
确定替莫唑胺联合沙利度胺治疗复发性GBM成人患者的6个月无进展生存期（6PFS）及毒性。
符合条件的患者为术后、放疗及/或辅助化疗后复发的GBM患者。替莫唑胺在每28天周期的第1 - 5天按150 - 200 mg/m²/天给药。沙利度胺于睡前口服400 mg（第1 - 28天），根据耐受情况增至1200 mg。每56天对患者进行磁共振成像扫描评估。该研究旨在检测GBM患者既往6PFS从10%提高至30%。
44例患者入组，43例可评估疗效和安全性。研究人群包括15名女性、29名男性；中位年龄53岁（范围32 - 84岁）；中位卡诺夫斯基功能状态为80%（范围60 - 100%）。36例（82%）患者未曾接受过化疗。有57例3级或更高级别毒性报告。15例患者（34%）出现非致命性3 - 4级粒细胞减少。客观缓解率为7%。该治疗方案6个月时无进展的估计概率为24% [95%置信区间（C.I.）1
