Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy - Results of a United Kingdom phase II trial (CNS 2007 04)
Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy - Results of a United Kingdom phase II trial (CNS 2007 04)
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DOI：
10.1016/j.ejca.2013.08.006
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发表时间：
2013-12-01
影响因子：
8.4
通讯作者：
Hargrave, D.
中科院分区：
文献类型：
--
作者：
Bailey, S.;Howman, A.;Hargrave, D.
弥漫性内在脑桥胶质瘤（DIPG）的预后很差，到目前为止还没有化疗方案，导致任何显着改善标准放疗。在这次审判中，为了克服O-6-甲基鸟嘌呤甲基转移酶（MGMT）介导的耐药，对43例临床放射学确诊为DIPG的患者进行了替莫唑胺延长治疗方案（21/28 d）的研究（75 mg/m2），然后给予辅助替莫唑胺（75-100 mg/m2），每周4次，最多12个疗程，每次21 d。该试验采用2阶段设计并通过中期分析，诊断时的中位年龄为8岁（2-20岁），81%有颅神经异常，76%有共济失调，57%有长束征。中位Karnofsky/Lansky评分为80（10-100）。患者接受了中位3个疗程的替莫唑胺辅助治疗，5例接受了所有12个疗程，7例未开始辅助治疗。3例患者因血液学毒性退出研究治疗，10例患者减量。未观察到与替莫唑胺相关的其他显著毒性。9个月时的总生存率（OS）（95%置信区间（CI））为56%（40%，69%），1年时为35%（21%，49%），2年时为17%（7%，30%）。中位生存期为9.5个月（范围7.5-11.4个月）。有5例2年生存者，诊断时的中位年龄为13.6岁。该试验表明，在经典DIPG儿童的标准放疗中加入剂量密集的替莫唑胺没有生存益处。然而，青少年DIPG患者的一个亚组确实有延长的生存期，这需要进一步探索。(C)2013作者由爱思唯尔有限公司出版。保留所有权利。
Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28 d) of temozolomide was studied with the aim of overcoming O-6-methylguanine methyltransferase (MGMT) mediated resistance.Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75 mg/m(2)) after which up to 12 courses of 21 d of adjuvant temozolomide (75-100 mg/m(2)) were given 4 weekly. The trial used a 2-stage design and passed interim analysis.At diagnosis median age was 8 years (2-20 years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10-100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9 months, 35% (21%, 49%) at 1 year and 17% (7%, 30%) at 2 years. Median survival was 9.5 months (range 7.5-11.4 months). There were five 2-year survivors with a median age of 13.6 years at diagnosis.This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.