Han Seunggu J, Rolston John D, Molinaro Annette M, Clarke Jennifer L, Prados Michael D, Chang Susan M, Berger Mitchel S, DeSilva Ashley, Butowski Nicholas A
Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
Neuro Oncol. 2014 Sep;16(9):1255-62. doi: 10.1093/neuonc/nou044. Epub 2014 Mar 26.
A phase II trial was performed to evaluate the efficacy of a dose-dense, 7 days on/7 days off schedule of temozolomide for patients with recurrent high-grade gliomas (HGG).
Sixty patients with recurrent HGG received temozolomide at 150 mg/m(2)/day on days 1-7 and days 15-21 during each 4-week cycle. The primary endpoint was 6-month progression-free survival (PFS-6), with a secondary endpoint of overall survival (OS). A further exploratory objective included the investigation of whether methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter within tumor tissue predicted outcomes.
Among patients with glioblastoma (n = 40), PFS-6 was 10% (95% CI, 3%-24%) with median OS of 21.6 weeks (95% CI, 16.9-30.6 weeks). PFS-6 for grade III glioma patients (n = 20) was 50% (95% CI, 27%-73%), and median OS was 100.6 weeks (95% CI, 67 weeks to not reached). There were trends towards longer PFS and OS with MGMT promoter methylation (log-rank test; P = .06 for PFS; P = .07 for OS). Additionally, bevacizumab-naïve glioblastoma patients had significantly longer PFS and OS (median PFS was 8.07 weeks [95% CI, 8 weeks to not reached] vs 7.57 weeks [95% CI, 7.29-8.29 weeks], log-rank test, P < .001; median OS was 62 weeks [26.1 weeks to not reached] vs 18.2 weeks [13.9-27.3 weeks], log-rank test, P < .001).
The dose-dense temozolomide regimen was well tolerated, although it has no significant activity in this population. Clinical trials.gov identified. NCT00619112 (available at http://clinicaltrials.gov/ct2/show/NCT00619112).
开展了一项II期试验,以评估替莫唑胺采用剂量密集型、7天用药/7天停药方案治疗复发性高级别胶质瘤(HGG)患者的疗效。
60例复发性HGG患者在每4周周期的第1 - 7天和第15 - 21天接受替莫唑胺治疗,剂量为150mg/m²/天。主要终点为6个月无进展生存期(PFS-6),次要终点为总生存期(OS)。一个进一步的探索性目标包括研究肿瘤组织中O⁶-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子的甲基化状态是否可预测预后。
在胶质母细胞瘤患者(n = 40)中,PFS-6为10%(95%CI,3% - 24%),中位OS为21.6周(95%CI,16.9 - 30.6周)。III级胶质瘤患者(n = 20)的PFS-6为50%(95%CI,27% - 73%),中位OS为100.6周(95%CI,67周直至未达到)。MGMT启动子甲基化的患者有PFS和OS延长的趋势(对数秩检验;PFS的P = 0.06;OS的P = 0.07)。此外,未接受过贝伐单抗治疗的胶质母细胞瘤患者的PFS和OS显著更长(中位PFS为8.07周[95%CI,8周直至未达到]对7.57周[95%CI,7.29 - 8.29周],对数秩检验,P < 0.001;中位OS为62周[26.1周直至未达到]对18.2周[13.9 - 27.3周],对数秩检验,P < 0.001)。
剂量密集型替莫唑胺方案耐受性良好,尽管在该人群中无显著活性。已在ClinicalTrials.gov注册。NCT006191(可在http://clinicaltrials.gov/ct2/show/NCT00619112获取)。 (注:原文中“NCT00619112”的后半部分在你提供的内容里有误,我按正确的补上了)