Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center, Randomized, Parallel, Open-label, Phase II Clinical Trial.
BACKGROUND
The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.


METHODS
A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS).


RESULTS
The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively.


CONCLUSIONS
Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.
Ying
Y
Mao
Yu
Y
Yao
Li-Wei
LW
Zhang
Yi-Cheng
YC
Lu
Zhong-Ping
ZP
Chen
Jian-Min
JM
Zhang
Song-Tao
ST
Qi
Chao
C
You
Ren-Zhi
RZ
Wang
Shu-Yuan
SY
Yang
Xiang
X
Zhang
Ji-Sheng
JS
Wang
Ju-Xiang
JX
Chen
Qun-Ying
QY
Yang
Hong
H
Shen
Zhi-Yong
ZY
Li
Xiang
X
Wang
Wen-Bin
WB
Ma
Xue-Jun
XJ
Yang
Hai-Ning
HN
Zhen
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Liang-Fu
LF
Zhou
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000379:methods*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008875:Middle Aged; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide