Zincircioglu S B, Kaplan M A, Isikdogan A, Cil T, Karadayi B, Dirier A, Kucukoner M, Inal A, Yildiz I, Aggil F, Donmez O, Urakci Z, Pekkolay Z, Firat U
Department of Radiation Oncology, Dicle University, Diyarbakir, Turkey.
J BUON. 2012 Jan-Mar;17(1):124-7.
Glioblastoma multiforme (GBM) is the most common brain tumor in adults and has a very aggressive course. Median survival is as short as 2 years with standard treatment (chemoradiotherapy followed by adjuvant temozolomide). The purpose of this study was to determine the contribution of low molecular weight heparin (LMWH) addition to concomitant chemoradiotherapy in the treatment of GBM.
All patients with newly diagnosed GBM between March 2004-May 2009 were evaluated. After surgical intervention (total, subtotal resection or only biopsy) all of them were treated with concomitant chemoradiotherapy (2 Gy daily, 5 days a week, 30 fractions, total tumor dose 60 Gy; and 75 mg/m² temozolomide, 7 days a week), followed by adjuvant temozolomide (6 cycles, 150-200 mg/m², 5 days every 28 days), with or without LMWH (4000 IU/day, 7 days a week, concomitant with radiotherapy) because of risk of thrombosis. The primary endpoint was the determination of progression-free survival (PFS) and overall survival (OS); secondary endpoints were 1- and 2-year OS survival.
30 patients (13 patients in the group non receiving LMWH (LMWH-) and 17 patients in the group receiving LMWH (LMWH+)) were included in the study. Median age was 54 years (range 24-75). Median PFS was 57 and 38 weeks in LMWH+ and LMWH- groups, respectively (p=0.068). Median OS was 69 and 44 weeks (p=0.095), 1-year OS survival 84.6 and 41.2% (p=0.016), and 2-year OS survival 38.5 and 5.9% in LMWH+ and LMWH-, respectively (p=0.061). No significant difference was noted between the two groups for grade 3-4 toxicity (p>0.05).
Better PFS, OS and 2-year OS survival were obtained in present study with the addition of LMWH to concomitant chemoradiation for GBM but without statistical significance. One-year OS survival was statistically significant favoring the LMWH group. The addition of LMWH did not increase temozolomide toxicity.
多形性胶质母细胞瘤（GBM）是成人中最常见的脑肿瘤，病程极具侵袭性。采用标准治疗（放化疗，随后辅助使用替莫唑胺）时，中位生存期短至2年。本研究的目的是确定在GBM治疗中添加低分子量肝素（LMWH）至同步放化疗的作用。
对2004年3月至2009年5月期间所有新诊断为GBM的患者进行评估。在手术干预（全切、次全切或仅活检）后，所有患者均接受同步放化疗（每日2 Gy，每周5天，共30次分割，肿瘤总剂量60 Gy；以及75 mg/m²替莫唑胺，每周7天），随后辅助使用替莫唑胺（6个周期，150 - 200 mg/m²，每28天5天），因有血栓形成风险，部分患者使用或不使用LMWH（4000 IU/天，每周7天，与放疗同时使用）。主要终点是确定无进展生存期（PFS）和总生存期（OS）；次要终点是1年和2年总生存率。
30例患者纳入研究（13例未接受LMWH的患者（LMWH -组）和17例接受LMWH的患者（LMWH +组））。中位年龄为54岁（范围24 - 75岁）。LMWH +组和LMWH -组的中位PFS分别为57周和38周（p = 0.068）。中位OS分别为69周和44周（p = 0.095），1年总生存率分别为84.6%和41.2%（p = 0.016），LMWH +组和LMWH -组的2年总生存率分别为38.5%和5.9%（p = 0.061）。两组3 - 4级毒性无显著差异（p>0.05）。
本研究中，在GBM同步放化疗中添加LMWH可获得更好的PFS、OS和2年总生存率，但无统计学意义。1年总生存率在统计学上有利于LMWH组。添加LMWH未增加替莫唑胺毒性。
