60岁及以下间变性星形细胞瘤或胶质母细胞瘤患者术后放疗前新辅助替莫唑胺与标准放疗的随机试验
Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial.
作者信息
Malmström Annika, Poulsen Hans Skovgaard, Grønberg Bjørn Henning, Stragliotto Giuseppe, Hansen Steinbjørn, Asklund Thomas, Holmlund Birgitta, Łysiak Małgorzata, Dowsett Joseph, Kristensen Bjarne Winther, Söderkvist Peter, Rosell Johan, Henriksson Roger
机构信息
a Department of Oncology , Linköping University Hospital , Linköping , Sweden.
b Department of Clinical and Experimental Medicine , Linköping University , Linköping , Sweden.
出版信息
Acta Oncol. 2017 Dec;56(12):1776-1785. doi: 10.1080/0284186X.2017.1332780. Epub 2017 Jul 4.
INTRODUCTION
A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.
PATIENTS AND METHODS
Patients, after surgery for GBM or AA, age ≤60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200 mg/m days 1-5 every 28 days, followed by RT 60 Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75 mg/m was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.
RESULTS
The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p = .76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p = .022). For patients with GBM, no difference in survival was observed (p = .10). MGMT and IDH status affected outcome.
CONCLUSIONS
No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.
引言
一项针对间变性星形细胞瘤（AA）和胶质母细胞瘤（GBM）患者在放疗（RT）前给予替莫唑胺（TMZ）的初步研究显示，与仅接受放疗的历史对照组相比，患者生存期延长。因此，我们在一项随机试验中研究了新辅助替莫唑胺（NeoTMZ）。在入组期间，TMZ同步放化疗成为标准治疗方案。该试验进行了修订，纳入了同步TMZ治疗。
患者与方法
对年龄≤60岁、体能状态（PS）为0 - 2的GBM或AA患者进行手术治疗后，将其随机分为两组，一组接受2 - 3个周期的TMZ治疗（200mg/m²，第1 - 5天，每28天为一个周期），随后接受60Gy、分30次的放疗；另一组仅接受放疗。在接受两个TMZ周期治疗后无疾病进展的患者接受第三个周期治疗。从2005年3月起，在放疗期间每日给予TMZ 75mg/m²。TMZ被推荐为疾病进展时的一线治疗。主要终点是总生存期，次要终点是安全性。
结果
在纳入144例患者（103例GBM患者和41例AA患者）后，该研究提前结束。中位年龄为53岁（范围24 - 60岁），89例（62%）为男性。133例（92%）患者的PS为0 - 1，53例（37%）患者接受了完整手术切除，18例（12%）患者接受了活检。92例（64%）患者在放疗期间接受了TMZ治疗。72例（50%）患者被随机分配接受新辅助治疗。对于整个研究人群，放疗组的生存期为20.3个月，NeoTMZ组为17.7个月（p = 0.76），未达到主要目标。在预先计划的亚组分析中，我们发现NeoTMZ组AA患者的中位生存期为95.1个月，而放疗组为35.2个月（p = 0.022）。对于GBM患者，未观察到生存期差异（p = 0.10）。MGMT和IDH状态影响预后。
结论
对于整个研究人群或GBM亚组，未发现NeoTMZ有优势，而对于诊断为AA的患者，NeoTMZ使中位生存期延长了5年。
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