Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03
Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03
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DOI：
10.1200/jco.2006.06.9104
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发表时间：
2006-09-20
影响因子：
45.3
通讯作者：
Weller, Michael
中科院分区：
文献类型：
--
作者：
Herrlinger, Ulrich;Rieger, Johannes;Weller, Michael
目的评价洛莫司汀、替莫唑胺(TMZ)和受累野放疗联合治疗新诊断的胶质母细胞瘤(GBM)的毒性和疗效。患者与方法两个中心31例成年患者(Karnofsky功能评分中位数90分，中位年龄51岁)接受受累野放疗(60Gy2次/次)和洛莫司汀100 mg/m(2)(D1)和TMZ 100 mg/m(2)/d(2~6天)化疗，根据血液学毒性进行个体化剂量调整。在5名患者(16%)中观察到WHO 4级血液毒性，其中1名患者死于败血症。非血液学毒性包括1例WHO 4级药物性肝炎(导致停用洛莫司汀和TMZ)和1例WHO 2级肺纤维化(导致停用洛莫司汀)。6个月无进展生存率(PFS)为61.3%。中位PFS为9个月(95%CI，5.3~11.7个月)，中位总生存期(MST)为22.6个月(95%CI，12.5个月为不可评估)，2年生存率为44.7%。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较长的PFS(P=.014，log-ranch检验)和MST(P=.037)相关。结论洛莫司汀、TMZ和放射治疗的联合应用对新诊断的GBM患者具有可接受的毒性和良好的生存数据。MGMT基因启动子甲基化是生存的有力预测因素。
PurposeTo evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM).Patients and MethodsThirty-one adult patients (median Karnofsky performance score 90, median age, 51 years) accrued in two centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and chemotherapy with lomustine 100 mg/m(2) (day 1) and TMZ 100 mg/m(2)/d (days 2 to 6) with individual dose adjustments according to hematologic toxicity.ResultsA median of five courses (range, one to six courses) were delivered. WHO grade 4 hematotoxicity was observed in five patients (16%) and one of these patients died as a result of septicemia. Nonhematologic toxicity included one patient with WHO grade 4 drug-induced hepatitis (leading to discontinuation of lomustine and TMZ) and one patient with WHO grade 2 lung fibrosis (leading to discontinuation of lomustine). The progression-free survival (PFS) rate at 6 months was 61.3%. The median PFS was 9 months (95% Cl, 5.3 to 11.7 months), the median overall survival time (MST) was 22.6 months (95% Cl, 12.5 to not assessable), the 2-year survival rate was 44.7%. O-6-Methylguanine-DNA methyltransferase (MGMT) gene-promoter methylation in the tumor tissue was associated with longer PFS (P =.014, log-rank test) and MST (P =.037).ConclusionThe combination of lomustine, TMZ, and radiotherapy had acceptable toxicity and yielded promising survival data in patients with newly diagnosed GBM. MGMT gene-promoter methylation was a strong predictor of survival.