颅内恶性胶质瘤术后替莫唑胺单纯化疗/联合放疗的疗效观察
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摘要
目的:
观察颅内恶性胶质瘤术后替莫唑胺单纯化疗/联合放疗的临床疗效。
方法:
2007年3月至2008年3月入组合格患者35例,随机分成三组。一组为空白对照组,一组接受单纯化疗,一组接受化疗联合放疗。按照体表面积给于替莫唑胺胶囊化疗。放疗方法按常规分割60Gy/30次。同时每月进行临床随访,定期复查头颅强化CT或MRI与化疗前资料比较判断病情变化。以化疗后影像学及临床功能变化来评价治疗效果,并比较两种方案的治疗效果。
结果:
影像学检查提示化疗后3个月空白对照组和单纯化疗组的无进展生存率分别为14.29%、66.67%(P＜0.05),单纯化疗组和联合治疗组的有效率分别为16.67%、66.67%(P＜0.05);临床功能状态检查提示化疗后3个月功能改善率为41.67%。
结论:
应用替莫唑胺在颅内恶性胶质瘤术后进行化疗可延缓肿瘤的增殖和复发,改善临床功能,是减少该类疾病术后复发和提高术后生存质量的有效方法。化疗与放疗联合治疗效果优于单纯化疗。
Objective:
To observe the clinical effect of temozolomide in chemotherapy only/in radio-chemotherapy combined treatment for intracal glioblastoma after operation.
Methods:
From Spring 2007 to Spring 2008,35 eligile patients were randomised to divided in three groups.One group did not accept any therapy,one groups accept exclusively chemotherapy,one groups accept radio-chemotherapy combined treatment.TMZ was administered according to the body area. Radiotherapy project is routine dissection 60Gy/30 times.Meantime clinical experience should be performed every a month,and contrast enhanced CT scan or GD-MRI was performed to evaluate image-based progression comparing with the image before chemotherapy.We evaluate the therapeutic efficacy according to the imageology and clinical functional changes after chemotherapy.
Results:
3 month after chemotherapy.the progression to survival rate of the blanck control group and the chemotherapy group is separately 14.29%、66.67%(P＜0.05)according to the imageology.Meantime,the effective power of the exclusively chemotherapy group and the radio-chemotherapy group is separately 16.67%、66.67%(P＜0.05).the improvement rate of clinical functional status 41.67%。
Conclusion:
The chemotherapy application of temozolomide in Intracal spongioblastoma can delay the generation and recrudescence of tumor,it also can improve the clinical function.so it is an effective method of reducing the post-operation recrudescence and elevating the living quality The effect of radio-chemotherapy combined treatment is better than exclusively chemotherapy.
观察颅内恶性胶质瘤术后替莫唑胺单纯化疗/联合放疗的临床疗效。
方法:
2007年3月至2008年3月入组合格患者35例,随机分成三组。一组为空白对照组,一组接受单纯化疗,一组接受化疗联合放疗。按照体表面积给于替莫唑胺胶囊化疗。放疗方法按常规分割60Gy/30次。同时每月进行临床随访,定期复查头颅强化CT或MRI与化疗前资料比较判断病情变化。以化疗后影像学及临床功能变化来评价治疗效果,并比较两种方案的治疗效果。
结果:
影像学检查提示化疗后3个月空白对照组和单纯化疗组的无进展生存率分别为14.29%、66.67%(P＜0.05),单纯化疗组和联合治疗组的有效率分别为16.67%、66.67%(P＜0.05);临床功能状态检查提示化疗后3个月功能改善率为41.67%。
结论:
应用替莫唑胺在颅内恶性胶质瘤术后进行化疗可延缓肿瘤的增殖和复发,改善临床功能,是减少该类疾病术后复发和提高术后生存质量的有效方法。化疗与放疗联合治疗效果优于单纯化疗。
Objective:
To observe the clinical effect of temozolomide in chemotherapy only/in radio-chemotherapy combined treatment for intracal glioblastoma after operation.
Methods:
From Spring 2007 to Spring 2008,35 eligile patients were randomised to divided in three groups.One group did not accept any therapy,one groups accept exclusively chemotherapy,one groups accept radio-chemotherapy combined treatment.TMZ was administered according to the body area. Radiotherapy project is routine dissection 60Gy/30 times.Meantime clinical experience should be performed every a month,and contrast enhanced CT scan or GD-MRI was performed to evaluate image-based progression comparing with the image before chemotherapy.We evaluate the therapeutic efficacy according to the imageology and clinical functional changes after chemotherapy.
Results:
3 month after chemotherapy.the progression to survival rate of the blanck control group and the chemotherapy group is separately 14.29%、66.67%(P＜0.05)according to the imageology.Meantime,the effective power of the exclusively chemotherapy group and the radio-chemotherapy group is separately 16.67%、66.67%(P＜0.05).the improvement rate of clinical functional status 41.67%。
Conclusion:
The chemotherapy application of temozolomide in Intracal spongioblastoma can delay the generation and recrudescence of tumor,it also can improve the clinical function.so it is an effective method of reducing the post-operation recrudescence and elevating the living quality The effect of radio-chemotherapy combined treatment is better than exclusively chemotherapy.
引文
1 Randes AA, Ermani M , Basso U , et al. Temozolomide as a second - line systemic regimen in recurrent high-grade glioma : a phase II study. Ann Onclo,2001,12 : 255-7
2 Stupp R , Dietrich P Y , Ostermann K , et al Promising survival for patients with newly diagnosed glioblatoma multiform treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide . J Clin onclo , 2002 ,20 :1375-82 .
3 Yung WK, Albright RE, Olson J, et al. A phase II study of temozolomide vs.procarbazine in patients with glioblastoma multiforme at first relapse . Br J Cancer, 2000,83:588-93.
4 Oliver-louis C , Stephan H , Henry D , et al . Safety and Efficacy of Temozolomide in patients with recurrent anaplastic Oligodendroglioma after standard radiotherapy and chemotherapy. J Clinical Onclogy, 200 1,19 : 2449-2455.
5 Antonadou D , Paraskevaidis M , Sarris G , et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Onclo , 2002,120 : 3644-3650.
6 Yung WK. Temozolomide in malignant gliomas. Semin Onclo, 2000,27 ( 3th Suppl 6): 35-40.
7 章翔主编.神经系统肿瘤学.北京,军事医学科学出版社,1999.192-195.
8 王忠诚主编.神经外科学.第2版,武汉:湖北科学技术出版社,1998.414
9 江涛主编.脑胶质瘤.北京,人民卫生出版社,2006.212
10 Macdonald DR.Temozolomide for recurrent high- grade glioma.Semin -Oncol,2001,28(4 Suppl 13):3-12.
11 王忠诚主编.神经外科学.第2版,武汉:湖北科学技术出版社,1998.215
12 Wong ET,Hess KR,Gleason MJ,et al.Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase Ⅱ clinical trials.J Clin Oncol,1999,17(8):2572-2578.
13 Yung WK,Prados MD,Yaya Tur R,et al.Multicenter phase Ⅱ trial of temozolomide in patients with anaplastic astrocytoma or anaplastic Oligoastrocytoma at first relapse.J Clin Oncol,1999,17(9):2762-2771.
14 Yung WK,Albright RE,Olson J,et al.A phase Ⅱ studyoftemozolomide vs.procarbazine in patients with gliobjastoma multiform at first relapse.Br J Cancer,2000,83(5):588-5893.
15 Janinis J,Efstathiou E,Panopoulos C,et al.Phase Ⅱ study of temozolomide in patients with relapsing high grade glioma and poor perrformance status.Med Onclo,2000.17:106-110.
16 陈步东,杨玉山.替莫唑胺治疗颅内恶性胶质瘤疗效观察[J].中国现代神经疾病杂志,2004,220-223.
17 曾宪起等.应用替莫唑胺对照司莫司丁治疗恶性胶质瘤的疗效观察[J]. 中华神经外科杂志, 2006, 204-207.
18 Brade M , Hoang Auan K , Rampling A. Multiccenter phase II trial of temozolomide in patients with gliblstome multiform at first replase. Ann Oncfo, 2001,12 :159 -166.
19 Harris M T, Rosenthal MA, Ashley DL, et al. An Australian exprience with Temozolomide for the treatment of recurrent high-grade gliomas . J Clin Neurosci. 2001,8 :325-327 .
20 Roger S, Mason W P, Martin J, et al. Radiotherapy plus concomitantand adjuvant temozolomode for glioblastoma[J]. N Engl J Med, 2005,352(10):987- 996.
21 Stupp R , Dietrich PY, Ostermann Kraljevic S , et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol, 2002 , 20 (5): 1375-1382.
22 Lanzetta G , Campanella C , Rozzi A , et al. Temozolomide in radio -chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme : phase II clinical trial . Anticancer Res , 2003 , 23 ( 6D ) :5159-5164.
23 Stupp R , Mason WP , van den Bent MJ , el al. Radiotherapy plus con-comitant and adjuvant temozolomide for glioblastom N Engl J Med ,2005 , 352 (10): 987-996.
24 Chen ZP, Malapetsa A, McQuillan A, et al. Evidence fornucleotide excision repairs a modifying factor of O6-methylguanine-DNA methyltransferasemediated innatechloroethylnitrosourea resistance in human tumor celllines [J].Mol Pharmacol,1997,52(5):815-820.
25 Jin P,Zhang QL,Liu FS,et al.Establishment of drug- resistancecell line of human glioma mediated by MGMT[J].Zhongguo Yi Xue Ke Xue Yuan Xue Bao,2002,24(6):596-600.
26 张俊平,史鸿浏,赛克,等.体外药敏试验及MGMT表达为依据的恶性胶质瘤个体化化疗:42例近期疗效分析[J].癌症,2006,25(12):1533-1537.
1 张纪.深入开展胶质瘤综合治疗及其基础研究[J].中华神经外科杂,2003,19(1):1-2.
2 王继跃,张士刚,孙学礼,等.脑胶质瘤的综合治疗。附72例临床分析[J].肿瘤防治杂志,2001 8:520-521.
3 陈忠平.脑胶质瘤治疗的新思路[J].广东医学,2000,21:809-811.
4 PAWLIK TM,KEYOMARSI K.Role of cell cycle inmediating sensitivity to radiotherapy[J].Int J Radiationcol Biol Phys,2004,59(4):928.
5 步星耀,赵红卫,胡明伟,等.脑胶质瘤术后敏感药物间质化疗联合增敏放疗的临床分析[J].实用诊断与治疗杂志,2004,18(3):168.
6 Deorah S,Lynch C F,Sibenaller Z A,et al.Trends in brain cancer incidence and survival in the United States:Surveillance,Epidemiology,and End Results Program,1973 to 2001[J].Neurosurg Focus,2006,20(4):E1.
7 Dandy W E.Removal of right cerebral hemisphere for certain tumors with hemiplegia:preliminary report.[J].JAMA,1928,90:823-825.
8 Reynolds B A,Tetzlaff W,Weiss S.A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes[J].J Neurosci,1992,12(11):4565- 4574.
9 Singh S K,Clarke I D,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors[J].Cancer Res,2003,63(18):5821-5828.
10 Singh S K,Hawkins C,Clarke I D,et al.Identification of human brain tumour initiating cells[J].Nature,2004,432(7015):396-401.
11 Udani V M,Santarelli J G,Yung Y C,et al.Hematopoietic stem cells give rise to perivascular
endothelial-like cells during brain tumor angiogenesis[J].Stem Cells Dev,2005,14(5):478-486.
12 Stewart L A.Chemotherapy in adult high-grade glioma:a systematic review and meta-analysis of individual patient data from 12randomised trials[J].Lancet,2002,359(9311):1011-1018.
13 陈忠平,周旺宁.胶质瘤的分子病理学特征与个体综合治疗决策[J].中华神经外科疾病研究杂志,2004,3(5):385-388.
14 Hutterer M,Gunsilius E,Stockhammer G.Molecular therapies for malignant glioma[J].Wien Med Wochenschr,2006,156(11-12):351-363.
15 孙俊平,史鸿浏,赛克,等.体外药敏试验及MGMT表达为依据的恶性胶质瘤个体化化疗:42例近期疗效分析[J].癌症,2006,25(12):1533-1537.
16 Liu G,Yuan X,Zeng Z,et al.Analysis of gene expression and chemoresistance of CD133+cancer stem cells in glioblastoma[J].Mol Cancer,2006,5:67-71.
17 张俊英,梁永钜,李永强,等.恶性脑肿瘤体外化疗药物敏感性试验初步报告[J].广东医学,2003,7(24):715-717.
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20 Stupp R,Mason W P,Van Den Bent M J,et al.Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma[J].N Engl J Med,2005,352(10):987-996.
21 陈忠平.神经肿瘤领域的新动态[J].中国神经肿瘤杂志,2005,3(4):233-236.
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34 Stewart L A.Chemotherapy in adult high- grade glioma:a systematic review and meta - analysis of individual patient data from 12 randomised trials[J].Lancet,2002,359(9311):1011-1018.
35 Roger S,Mason W P,Martin J,et al.Radiotherapy plus concomitant and adjuvant temozolomode for glioblastoma[J].N Engl J Med,2005,352(10):987-996.
36 Eyre H J,Crowley J J,Townsend J J,et al.A randomized trial of radiotherapy versus radiotherapy plus CCNU for incompletely resected lowgrade gliomas:a Southwest Oncology Group study[J].J Neurosurg,1993,78(6):909-914.
2 Stupp R , Dietrich P Y , Ostermann K , et al Promising survival for patients with newly diagnosed glioblatoma multiform treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide . J Clin onclo , 2002 ,20 :1375-82 .
3 Yung WK, Albright RE, Olson J, et al. A phase II study of temozolomide vs.procarbazine in patients with glioblastoma multiforme at first relapse . Br J Cancer, 2000,83:588-93.
4 Oliver-louis C , Stephan H , Henry D , et al . Safety and Efficacy of Temozolomide in patients with recurrent anaplastic Oligodendroglioma after standard radiotherapy and chemotherapy. J Clinical Onclogy, 200 1,19 : 2449-2455.
5 Antonadou D , Paraskevaidis M , Sarris G , et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Onclo , 2002,120 : 3644-3650.
6 Yung WK. Temozolomide in malignant gliomas. Semin Onclo, 2000,27 ( 3th Suppl 6): 35-40.
7 章翔主编.神经系统肿瘤学.北京,军事医学科学出版社,1999.192-195.
8 王忠诚主编.神经外科学.第2版,武汉:湖北科学技术出版社,1998.414
9 江涛主编.脑胶质瘤.北京,人民卫生出版社,2006.212
10 Macdonald DR.Temozolomide for recurrent high- grade glioma.Semin -Oncol,2001,28(4 Suppl 13):3-12.
11 王忠诚主编.神经外科学.第2版,武汉:湖北科学技术出版社,1998.215
12 Wong ET,Hess KR,Gleason MJ,et al.Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase Ⅱ clinical trials.J Clin Oncol,1999,17(8):2572-2578.
13 Yung WK,Prados MD,Yaya Tur R,et al.Multicenter phase Ⅱ trial of temozolomide in patients with anaplastic astrocytoma or anaplastic Oligoastrocytoma at first relapse.J Clin Oncol,1999,17(9):2762-2771.
14 Yung WK,Albright RE,Olson J,et al.A phase Ⅱ studyoftemozolomide vs.procarbazine in patients with gliobjastoma multiform at first relapse.Br J Cancer,2000,83(5):588-5893.
15 Janinis J,Efstathiou E,Panopoulos C,et al.Phase Ⅱ study of temozolomide in patients with relapsing high grade glioma and poor perrformance status.Med Onclo,2000.17:106-110.
16 陈步东,杨玉山.替莫唑胺治疗颅内恶性胶质瘤疗效观察[J].中国现代神经疾病杂志,2004,220-223.
17 曾宪起等.应用替莫唑胺对照司莫司丁治疗恶性胶质瘤的疗效观察[J]. 中华神经外科杂志, 2006, 204-207.
18 Brade M , Hoang Auan K , Rampling A. Multiccenter phase II trial of temozolomide in patients with gliblstome multiform at first replase. Ann Oncfo, 2001,12 :159 -166.
19 Harris M T, Rosenthal MA, Ashley DL, et al. An Australian exprience with Temozolomide for the treatment of recurrent high-grade gliomas . J Clin Neurosci. 2001,8 :325-327 .
20 Roger S, Mason W P, Martin J, et al. Radiotherapy plus concomitantand adjuvant temozolomode for glioblastoma[J]. N Engl J Med, 2005,352(10):987- 996.
21 Stupp R , Dietrich PY, Ostermann Kraljevic S , et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol, 2002 , 20 (5): 1375-1382.
22 Lanzetta G , Campanella C , Rozzi A , et al. Temozolomide in radio -chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme : phase II clinical trial . Anticancer Res , 2003 , 23 ( 6D ) :5159-5164.
23 Stupp R , Mason WP , van den Bent MJ , el al. Radiotherapy plus con-comitant and adjuvant temozolomide for glioblastom N Engl J Med ,2005 , 352 (10): 987-996.
24 Chen ZP, Malapetsa A, McQuillan A, et al. Evidence fornucleotide excision repairs a modifying factor of O6-methylguanine-DNA methyltransferasemediated innatechloroethylnitrosourea resistance in human tumor celllines [J].Mol Pharmacol,1997,52(5):815-820.
25 Jin P,Zhang QL,Liu FS,et al.Establishment of drug- resistancecell line of human glioma mediated by MGMT[J].Zhongguo Yi Xue Ke Xue Yuan Xue Bao,2002,24(6):596-600.
26 张俊平,史鸿浏,赛克,等.体外药敏试验及MGMT表达为依据的恶性胶质瘤个体化化疗:42例近期疗效分析[J].癌症,2006,25(12):1533-1537.
1 张纪.深入开展胶质瘤综合治疗及其基础研究[J].中华神经外科杂,2003,19(1):1-2.
2 王继跃,张士刚,孙学礼,等.脑胶质瘤的综合治疗。附72例临床分析[J].肿瘤防治杂志,2001 8:520-521.
3 陈忠平.脑胶质瘤治疗的新思路[J].广东医学,2000,21:809-811.
4 PAWLIK TM,KEYOMARSI K.Role of cell cycle inmediating sensitivity to radiotherapy[J].Int J Radiationcol Biol Phys,2004,59(4):928.
5 步星耀,赵红卫,胡明伟,等.脑胶质瘤术后敏感药物间质化疗联合增敏放疗的临床分析[J].实用诊断与治疗杂志,2004,18(3):168.
6 Deorah S,Lynch C F,Sibenaller Z A,et al.Trends in brain cancer incidence and survival in the United States:Surveillance,Epidemiology,and End Results Program,1973 to 2001[J].Neurosurg Focus,2006,20(4):E1.
7 Dandy W E.Removal of right cerebral hemisphere for certain tumors with hemiplegia:preliminary report.[J].JAMA,1928,90:823-825.
8 Reynolds B A,Tetzlaff W,Weiss S.A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes[J].J Neurosci,1992,12(11):4565- 4574.
9 Singh S K,Clarke I D,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors[J].Cancer Res,2003,63(18):5821-5828.
10 Singh S K,Hawkins C,Clarke I D,et al.Identification of human brain tumour initiating cells[J].Nature,2004,432(7015):396-401.
11 Udani V M,Santarelli J G,Yung Y C,et al.Hematopoietic stem cells give rise to perivascular
endothelial-like cells during brain tumor angiogenesis[J].Stem Cells Dev,2005,14(5):478-486.
12 Stewart L A.Chemotherapy in adult high-grade glioma:a systematic review and meta-analysis of individual patient data from 12randomised trials[J].Lancet,2002,359(9311):1011-1018.
13 陈忠平,周旺宁.胶质瘤的分子病理学特征与个体综合治疗决策[J].中华神经外科疾病研究杂志,2004,3(5):385-388.
14 Hutterer M,Gunsilius E,Stockhammer G.Molecular therapies for malignant glioma[J].Wien Med Wochenschr,2006,156(11-12):351-363.
15 孙俊平,史鸿浏,赛克,等.体外药敏试验及MGMT表达为依据的恶性胶质瘤个体化化疗:42例近期疗效分析[J].癌症,2006,25(12):1533-1537.
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