Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas
Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas
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DOI：
10.1093/annonc/mdg371
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发表时间：
2003-12-01
影响因子：
50.5
通讯作者：
Westbury, C
中科院分区：
文献类型：
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作者：
Brada, M;Viviers, L;Westbury, C
工作背景：本研究的目的是评估替莫唑胺在世界卫生组织（WHO）11级胶质瘤患者中的疗效，该患者仅使用成像和临床标准进行手术治疗。30例经组织学证实的WHO 11级胶质瘤患者（17例星形细胞瘤，11例少突胶质细胞瘤，2例混合性寡星形细胞瘤）术后2-104个月（中位23个月）在初次诊断后接受替莫唑胺200 mg/m2/天治疗5天，28天为一周期，最多12个周期或直至肿瘤进展。中位年龄为40岁（范围25-68岁）。从进入研究开始的中位随访时间为3年[范围为23-47个月（对于存活患者）]。通过3个月一次的磁共振成像和每月一次的健康相关生活质量（HQoL）和临床评估评估客观缓解。肿瘤大小测量为流体衰减反转恢复序列上的高信号强度区域。结果：30例患者中有29例可评价疗效，其中10例为完全缓解（CR）、部分缓解（PR）、最小缓解（MR）、疾病稳定（SD）和疾病进展（PD）。3例患者有PR，14例MR，11例SD和1例PD。24例患者接受了12个周期的化疗。在29例可评价患者中，3例在4、5和6个周期后停药，2例在10个周期后停药。9例患者进展（3例在化疗期间，1例PD和2例初始SD，6例在化疗完成后）; 5例有转化证据。3年无进展生存率为66%。5例患者死亡，3年生存率为82%。96%的HQoL受损患者至少在一个HQoL领域有改善。在207个领域中，有115个领域（56%）有所改善。28例癫痫患者中有15例（54%）癫痫发作频率降低，其中6例无癫痫发作。6例患者有短暂的III/IV级血液学毒性（11次发作; 3.5%）。结论：替莫唑胺具有单药活性的WHO 11级脑胶质瘤患者，适度改善生活质量和改善癫痫控制。根据目前的证据，在没有与其他治疗方式进行正式比较的情况下，不能将替莫唑胺视为主要治疗。
Background: The aim of this study was to assess the efficacy of temozolomide in patients with World Health Organisation (WHO) grade 11 gliomas treated with surgery alone using imaging and clinical criteria.Patients and methods: Thirty patients with histologically verified WHO grade 11 gliomas (17 astrocytoma, I I oligodendroglioma, two mixed oligoastrocytoma) following surgery 2-104 months (median 23 months) after initial diagnosis received temozolomide 200 mg/m(2)/day for 5 days, on a 28-day cycle, for a maximum of 12 cycles or until tumour progression. Median age was 40 years (range 25-68 years). Median follow-up from entry into the study was 3 years [range 23-47 months (for patients alive)]. Objective response was assessed by 3-monthly magnetic resonance imaging and monthly health-related quality of life (HQoL) and clinical assessment. Tumour size was measured as the high signal intensity area on fluid attenuated inversion recovery sequences. Responses were assessed using change in the product of two perpendicular diameters as complete response (CR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD).Results: Twenty-nine of 30 patients entered into the study were evaluable for response. Three patients had a PR, 14 MR, I I SD and one PD. Twenty-four patients received 12 cycles of chemotherapy. Of 29 evaluable patients, three discontinued after four, five and six cycles and two after 10 cycles. Nine patients progressed (three during chemotherapy-one PD and two initial SD-and six after completion of chemotherapy); five had evidence of transformation. The 3-year progression-free survival was 66%. Five patients died; the actuarial 3-year survival was 82%. Ninety-six per cent of patients with impaired HQoL had improvement in at least one HQoL domain. There was improvement in 115 of the 207 domains (56%). Fifteen of 28 patients (54%) with epilepsy had reduction in seizure frequency, of whom six became seizure free. Six patients had transient grade III/IV haematological toxicity (11 episodes; 3.5%).Conclusions: Temozolomide has single-agent activity in patients with WHO grade 11 cerebral glioma, with modest improvement in quality of life and improvement in epilepsy control. On present evidence, temozolomide cannot be considered as primary therapy without formal comparison with other treatment modalities.