Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine Plus Temozolomide
Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine Plus Temozolomide
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DOI：
10.1200/jco.2008.19.2195
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发表时间：
2009-03-10
影响因子：
45.3
通讯作者：
Herrlinger, Ulrich
中科院分区：
文献类型：
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作者：
Glas, Martin;Happold, Caroline;Herrlinger, Ulrich
PurposeTo评估一系列新诊断胶质母细胞瘤患者的长期生存率，这些患者接受洛莫司汀（CCNU）、替莫唑胺（TMZ）和放疗的联合治疗。患者和方法39例患者仅接受肿瘤部位放疗（60戈伊）和CCNU/TMZ化疗（31例接受标准剂量环己亚硝脲100 mg/m2，第1天;替莫唑胺100 mg/m2，第2 ~ 6天; 8例接受CCNU 110 mg/m2，第1天; TMZ 150 mg/m2，第2 ~ 6天，共6个疗程。术后2年生存率为47.4%，4年生存率为18.5%。中位随访41.5个月后，强化组未达到mOS，且显著高于标准组（22.6个月; P = 0.024）。在强化组中，8名患者中有4名存活至少56个月，其中2名没有复发。肿瘤组织中O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因启动子甲基化与显著更长的mOS相关（甲基化，34.3个月vs非甲基化，12.5个月）。多变量考克斯比例风险模型显示MGMT状态（甲基化vs非甲基化;死亡相对风险[RR]，0.43; P = 0.003）和化疗剂量（强化vs标准; RR，0.37; P = 0.012）是独立的预后因素。WHO 4级血液毒性观察到更频繁的强化group.ConclusionThe放疗，CCNU，TMZ的组合，新诊断的胶质母细胞瘤患者的长期生存数据（57%v 16%）。加强CCNU/TMZ化疗可能会增加额外的生存获益，尽管急性毒性更大。
PurposeTo evaluate long-term survival in a prospective series of patients newly diagnosed with glioblastoma and treated with a combination of lomustine (CCNU), temozolomide (TMZ), and radiotherapy.Patients and MethodsThirty-nine patients received radiotherapy of the tumor site only (60 Gy) and CCNU/TMZ chemotherapy (n = 31 received standard- dose CCNU, 100 mg/m(2) on day 1 and TMZ 100 mg/m(2)/d on days 2 to 6; n = 8 received intensified-dose CCNU 110 mg/m(2) on day 1 and TMZ 150 mg/m(2) on days 2 to 6) for up to six courses.ResultsIn the whole cohort, the median overall survival (mOS) was 23.1 months; 47.4% survived for 2 years, and 18.5% survived for 4 years. After a median follow-up of 41.5 months, mOS had not been reached in the intensified group and was significantly higher than in the standard group (22.6 months; P = .024). In the intensified group, four of eight patients survived for at least 56 months, two of them without recurrence. O-6-methylguanine-DNA methyltransferase (MGMT) gene promotor methylation in the tumor tissue was associated with significantly longer mOS (methylated, 34.3 months v nonmethylated, 12.5 months). A multivariate Cox proportional hazard model revealed MGMT status (methylated v nonmethylated; relative risk [RR] of death, 0.43; P = .003) and chemotherapy dose (intensified v standard; RR, 0.37; P = .012) as independent prognostic factors. WHO grade 4 hematoxicity was observed more frequently in the intensified group (57% v 16%).ConclusionThe combination of radiotherapy, CCNU, and TMZ yielded promising long-term survival data in patients with newly diagnosed glioblastoma. Intensification of CCNU/TMZ chemotherapy may add an additional survival benefit, albeit with greater acute toxicity.