Prados Michael D, Yung W K Alfred, Fine Howard A, Greenberg Harry S, Junck Larry, Chang Susan M, Nicholas M Kelly, Robins H Ian, Mehta Minesh P, Fink Karen L, Jaeckle Kurt A, Kuhn John, Hess Kenneth R, Schold S Clifford
Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA 94143, USA.
Neuro Oncol. 2004 Jan;6(1):33-7. doi: 10.1215/S1152851703000309.
The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m(2) i.v. followed in 2 h by temozolomide 550 mg/m(2) as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.
本研究旨在评估1,3-双（氯乙基）-1-亚硝基脲（BCNU）联合替莫唑胺对多形性胶质母细胞瘤复发成年患者的活性，活性通过无进展生存期（PFS）和缓解率来衡量。该试验的2期剂量和给药方案为：静脉注射BCNU 150 mg/m²，2小时后口服替莫唑胺550 mg/m²作为单次剂量。每6周重复治疗，最多8个周期，除非记录到肿瘤进展。主要终点是6个月时的PFS（PFS-6）。缓解是次要终点，通过每6周周期前的磁共振成像、神经状态和类固醇需求来衡量。符合条件患者的中位年龄为53岁，89.5%的患者既往未接受过化疗。所有患者均可评估毒性和疾病进展时间。PFS-6为21%。6个月时总生存率为68%，一年时为26%。36例患者的MRI缓解情况为2例部分缓解、2例轻微缓解、19例病情稳定和13例迅速进展。中位生存期为34周，中位PFS为11周。毒性主要为骨髓抑制；未发生毒性死亡。该患者群体既往2期研究数据显示PFS-6为15%。近期单独使用替莫唑胺的数据显示PFS-6为21%。我们得出结论，BCNU联合替莫唑胺按这些剂量和方案使用时活性有限，毒性显著，且似乎并不比单药替莫唑胺更有效。
