Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 Tiantan Xili, Dongcheng District, Beijing, 100050, China.
Neurosurg Rev. 2014 Jan;37(1):73-8. doi: 10.1007/s10143-013-0490-x. Epub 2013 Aug 3.
Although temozolomide (TMZ) replaced nitrosoureas as the standard initial chemotherapy for glioblastoma (GBM), no studies have compared TMZ with nimustine (ACNU), a nitrosourea agent widely used in central Europe and most Asian regions. One hundred thirty-five patients with GBM who underwent extensive tumor resection in our institution received both radiation and chemotherapy as initial treatment, 34 received TMZ and 101 ACNU-based (ACNU plus teniposide or cisplatin) chemotherapy. Efficacy analysis included overall survival (OS) and progression-free survival (PFS). The following prognostic factors were taken into account: age, performance status, extent of resection, and O(6)-methylguanine-DNA-methyltransferase (MGMT) gene status. The median OS was superior in the TMZ versus the ACNU group (p = 0.011), although MGMT gene silencing, which is associated with a striking survival benefit from alkylating agents, was more frequent in the ACNU group. In multivariate Cox analysis adjusting for the common prognostic factors, TMZ chemotherapy independently predicted a favorable outcome (p = 0.002 for OS, hazard ratio [HR], 0.45; p = 0.011 for PFS, HR, 0.56). Given that >40 % of patients in ACNU group did not receive the intensive chemotherapy cycles because of severe hematological and nonhematological toxicity, we performed a further subanalysis for patients who received at least 4 cycles of chemotherapy. Although a modest improvement in survival occurred in this ACNU subgroup, the efficacy was still inferior to that in the TMZ cohort. Our data suggest that the survival benefit of TMZ therapy is superior to that of an ACNU-based regimen in patients with extensive tumor resection, also shows greater tolerability.
虽然替莫唑胺（TMZ）已取代亚硝脲类药物成为胶质母细胞瘤（GBM）的标准初始化疗药物，但尚无研究比较 TMZ 与尼莫司汀（ACNU），后者是一种在中欧和亚洲大部分地区广泛使用的亚硝脲类药物。在我们机构，135 名接受广泛肿瘤切除术的 GBM 患者接受了放疗和化疗作为初始治疗，其中 34 名接受 TMZ 治疗，101 名接受 ACNU 治疗（ACNU 加依托泊苷或顺铂）。疗效分析包括总生存期（OS）和无进展生存期（PFS）。考虑了以下预后因素：年龄、表现状态、切除程度和 O(6)-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）基因状态。TMZ 组的中位 OS 优于 ACNU 组（p=0.011），尽管 ACNU 组中更频繁地出现 MGMT 基因沉默，这与烷化剂治疗的显著生存获益相关。在调整常见预后因素的多变量 Cox 分析中，TMZ 化疗独立预测了有利的结果（OS 的 p=0.002，风险比[HR]为 0.45；PFS 的 p=0.011，HR 为 0.56）。鉴于 ACNU 组中 >40%的患者因严重血液学和非血液学毒性而未接受强化化疗周期，我们对接受至少 4 个化疗周期的患者进行了进一步的亚组分析。尽管该 ACNU 亚组的生存略有改善，但疗效仍不如 TMZ 组。我们的数据表明，在广泛肿瘤切除的患者中，TMZ 治疗的生存获益优于 ACNU 方案，且具有更好的耐受性。
