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顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤临床研究

作者 / Author:韩小兵

摘要 / Abstract:

目的 探讨顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤患者的疗效及对其生活质量的影响。方法 选取我院63例复发性恶性脑胶质瘤患者随机分组,对照组31例,观察组32例,对照组予以替莫唑胺治疗,观察组予以顺铂+替莫唑胺治疗,观察比较临床疗效、生活质量评分及不良反应发生情况。结果 观察组缓解率为71.88%(23/32)、控制率为87.50%(28/32),高于对照组45.16%(14/31)、64.52%(20/31),差异具有统计学意义(P<0.05);治疗后观察组生活质量各指标评分均高于对照组,差异具有统计学意

关键词 / KeyWords:

顺铂,替莫唑胺,复发性恶性脑胶质瘤,生活质量,缓解率,恶性肿瘤
顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤临床研究
韩小兵
信阳市中心医院肿瘤内科,河南 信阳 464000
作者简介:韩小兵,Email:626132599@qq.com
摘要 目的 探讨顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤患者的疗效及对其生活质量的影响。方法 选取我院63例复发性恶性脑胶质瘤患者随机分组,对照组31例,观察组32例,对照组予以替莫唑胺治疗,观察组予以顺铂+替莫唑胺治疗,观察比较临床疗效、生活质量评分及不良反应发生情况。结果 观察组缓解率为71.88%(23/32)、控制率为87.50%(28/32),高于对照组45.16%(14/31)、64.52%(20/31),差异具有统计学意义(P<0.05);治疗后观察组生活质量各指标评分均高于对照组,差异具有统计学意义(P<0.05);观察组不良反应发生率为21.88%(7/32),对照组为12.90%(4/31),组间对比差异无统计学意义(P>0.05)。结论 顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤,疗效显著,可有效改善患者生活质量,安全性高。
关键词】 顺铂;替莫唑胺;复发性恶性脑胶质瘤;生活质量;缓解率;恶性肿瘤
中图分类号】 R739.41  【文献标识码】 A  【文章编号】 1673-5110(2018)18-2039-08  DOI:10.12083/SYSJ.2018.18.448
Clincal study on cisplatin combined with temozolomide in the treatment of recurrent malignant glioma
HAN Xiaobing
Department of OncologyXinyang Central HospitalXinyang 464000,China
Abstract】 Objective To evaluate the efficacy of cisplatin combined with temozolomide in the treatment of recurrent malignant glioma and its influence on the quality of life.Methods 63 cases of recurrent malignant glioma in our hospital were randomly divided into control group(n=31) and observation group(n=32).The control group was treated with temozolomide,and the observation group was treated with cisplatin combined with temozolomide.The clinical efficacy,quality of life score and adverse reactions were observed and compared.Results The remission rate of the observation group 71.88% (23/32) and the control rate 87.50% (28/32),which were higher than those of the control group 45.16% (14/31) and 64.52% (20/31),the difference was statistically significant (P<0.05).After treatment,the quality of life indicators in the observation group were higher than those in the control group,the difference was statistically significant (P<0.05).The incidence of adverse reactions was 21.88% (7/32) in the observation group and 12.90% (4/31)in the control group.There was no significant difference between the two groups (P>0.05).Conclusion Cisplatin combined with temozolomide is effective in the treatment of recurrent malignant glioma.It can effectively improve the quality of life of patients with high safety.
Key words】 Cisplatin;Temozolomide;Recurrent malignant glioma;Quality of life;Remission rate;Malignancy
    脑胶质瘤为临床常见恶性肿瘤之一,发病率较高,占全部颅内肿瘤的40%~50%,恶性脑胶质瘤多呈浸润性生长,预后效果差,手术难以彻底清除,导致其复发率极高[1-8]。而复发性恶性脑胶质瘤侵袭性更强、生长速度更快,致死率极高,对患者生命安全造成极大威胁。替莫唑胺为常用抗肿瘤药物,可通过阻断DNA合成,发挥抗肿瘤作用,控制病情进展,但其对复发性恶性脑胶质瘤效果不甚理想,有学者指出采用替莫唑胺与铂类药物联合治疗复发性恶性肿瘤效果更优,可有效改善患者临床症状,控制癌灶扩散,延长患者生存时间[9-15]。本研究选取63例复发性恶性脑胶质瘤患者分为2组,并予以不同药物治疗,观察顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤患者的疗效及对其生活质量的影响。
1 资料和方法
1.1 一般资料 选取我院2013-09—2016-10收治的63例复发性恶性脑胶质瘤患者随机分组,对照组31例,男20例,女11例,年龄37~60(52.31±6.19)岁,病程5~13(7.32±2.21)个月;观察组32例,男19例,女13例,年龄36~60(51.29±6.21)岁,病程7~17(9.29±2.24)个月。对比2组性别、病程、年龄等基线资料,差异无统计学意义(P>0.05),具有可比性。
1.2 纳入及排除标准 (1)纳入标准:符合第8版《外科学》中脑胶质瘤诊断标准[4];经病理证实为Ⅲ或Ⅳ级脑胶质瘤;经CT或MRI检查证实为复发性脑胶质瘤;知晓本研究并签署知情同意书。(2)排除标准:血小板计数<100×109/L;血红蛋白不足100 g/L者;预计生存期不足6个月者;合并血液系统疾病或心肾功能异常者;存在精神疾病或其他因素导致难以完成本研究者。
1.3 方法 对照组第1~28天晨起空腹口服替莫唑胺胶囊(江苏天士力帝益药业有限公司,国药准字H20040637)治疗,150 mg/m2,1次/d;若患者无较重骨髓抑制出现则增加剂量至200 mg/m2,连用4周。观察组于以上治疗基础上静脉滴注30 mg/m2顺铂(德州德药制药有限公司,国药准字H37020524)治疗,用药期间每天静脉滴注100 mL氯化钠溶液(0.9%)+5 mg盐酸托烷司琼注射液治疗,日补液量为2 500 mL及以上,静滴碳酸氢钠注射液(5%),1次/d碱化治疗,用药期间及用药后1 d静滴125 mL甘露醇治疗,疗程3个月。
1.4 观察指标 (1)治疗3个月后统计比较2组临床治疗效果。以实体瘤疗效评价标准(response evaluation criteria in solid tumors,RECIST)评估临床疗效:治疗3个月后出现新病灶或病灶体积增大25%及以上为进展;治疗后病情较治疗前无改善,病灶体积增大不足25%,或病灶体积缩小不足50%为稳定;病灶体积缩小50%及以上且持续1个月以上为部分缓解;治疗后临床症状完全消失,病灶基本消失,且维持1个月以上为完全缓解[16-25]。控制率=(稳定+部分缓解+完全缓解)/总例数×100%;缓解率=(部分缓解+完全缓解)/总例数×100%。(2)采用生活质量评分量表(short form 36 questionnaire,SF-36)对2组治疗前后生活质量进行评分比较,评分指标包含躯体角色、躯体功能、生命力、社会功能、心理职能、健康状况、机体疼痛、情感角色8个方面,得分越高,生活质量越好[26-37]。(3)统计比较2组用药后呕吐、恶心、骨髓抑制、脱发等不良反应发生情况。
1.5 统计学分析 通过SPSS 19.0对数据进行分析,计量资料以均数±标准差(x±s)表示,采用t检验,计数资料以率(%)表示,采用卡方检验,P<0.05为差异有统计学意义。
2 结果
2.1 2组疗效对比 观察组疾病缓解率、控制率均高于对照组,差异具有统计学意义(P<0.05)。见表1。
2.2 2组生活质量评分对比 治疗前2组生活质量各指标评分对比,差异无统计学意义(P>0.05),治疗后观察组生活质量各指标水平均高于对照组,差异具有统计学意义(P<0.05)。见表2。
表1 2组疗效对比 [n(%)]
Table 1 Comparison of the efficacy of the two groups  [n(%)]
组别 n 进展 稳定 部分缓解 完全缓解 缓解率/% 控制率/%
观察组 32 4(12.50) 5(15.63) 14(43.75) 9(28.13) 71.88(23/32) 87.50(28/32)
对照组 31 11(35.48) 6(19.35) 9(29.03) 5(16.13) 45.16(14/31) 64.52(20/32)
χ2         4.636   4.585
P         <0.05   <0.05
表2 2组治疗前后生活质量评分对比 (x±s,分)
Table 2 Comparison of quality of life scores before and after treatment in 2 groups (x±s,分)
时间 组别 n 躯体功能 躯体角色 生命力 心理职能 社会功能 健康状况 情感角色 机体疼痛
治疗前 观察组 32 59.21±2.15 57.32±6.06 59.22±7.09 56.61±4.37 64.39±25.01 45.47±13.13 52.88±13.02 55.72±4.25
  对照组 31 60.20±1.84 56.21±6.17 60.34±6.98 55.33±4.06 66.41±23.40 44.79±14.04 55.35±5.16 54.45±3.96
t   1.961 0.72 0.632 1.204 0.331 0.199 0.984 1.226
P   >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
治疗后 观察组 32 77.42±5.04 76.26±6.02 79.17±7.14 79.22±10.48 79.17±15.72 75.46±6.34 68.42±17.82 71.48±4.56
  对照组 31 65.32±3.01 68.13±6.25 68.34±5.40 68.21±10.15 67.15±14.24 68.36±6.68 59.21±5.29 60.59±5.75
t   11.522 5.259 6.774 4.234 3.178 4.328 2.762 8.343
P   <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
2.3 2组不良反应发生情况比较 观察组不良反应发生率为21.88(7/32),对照组为12.90%(4/31),组间对比差异无统计学意义(P>0.05)。见表3。
表3 2组不良反应发生率对比 [n(%)]
Table 3 Comparison of incidence rates of adverse reactions in 2 groups [n(%)]
组别 n 呕吐 脱发 恶心 骨髓抑制 总发生率/%
观察组 32 2(6.25) 1(3.13) 3(9.38) 1(3.13) 21.88
对照组 31 1(3.23) 0 2(6.45) 1(3.23) 12.9
χ2           0.88
P           >0.05
3 讨论
    复发性恶性脑胶质瘤为恶性程度较高的颅内占位性脑肿瘤,具有恶性程度高、病情重、病情进展快、预后差、复发率高等特点,已成为威胁人类健康的主要疾病之一[38-42]。手术为目前临床治疗恶性肿瘤常用方法,可有效切除病灶,但需保留患者重要神经中枢,难以彻底清除肿瘤组织,术后复发率高,相关数据显示其复发后5 a存活率不足10%,中位生存时间低至12~15个月[43-64]。如何控制病情恶化,降低复发率,延长患者生存时间,提高其生存质量已成为目前临床研究重点。
    替莫唑胺为非特异性周期性新型烷化剂,具有亲脂性好、分子量小、生物利用度高等特点,口服后,可快速被消化道吸收,生物利用度高[65-74],几乎100%药物剂量可进入血液,于血液中自行水解为5-咪唑-4-酰胺,并进一步降解生成重氮甲烷及5-氨基-咪唑-4-酰胺等抗肿瘤药物,导致DNA复制过程中出现错配,促使DNA双链及单链断裂,损伤DNA,而被损伤的DNA积聚于细胞内,压迫细胞,激活细胞凋亡通路,进而促使肿瘤细胞凋亡,延长患者生存时间[75-91];且其毒副作用小,仅有7%患者出现血液学毒性等不良反应,改善预后。卢喜卫等[20]采用顺铂联合替莫唑胺及同期放疗治疗术后胶质母细胞瘤,取得显著效果,治疗后患者1 a生存率高达81.25%,骨髓抑制发生率仅为13.89%。这可能是因为顺铂具有较强放射增敏作用,其通过抑制干扰肿瘤细胞放疗后亚致死性损伤修复,发挥协同作用,提高疗效[92-106];且其可作用于细胞DNA合成期,促使肿瘤细胞周期同步化,进而达到化疗增敏的目的[107-112];此外其可通过激活毛细血管扩张性共济失调症突变基因,改善肿瘤放射敏感性,杀伤肿瘤细胞,发挥抗肿瘤作用,控制疾病进展;与替莫唑胺联合使用,发挥药物间协同,提高疗效[113-114]。本研究结果显示,观察组疾病缓解率及控制率均高于对照组(P<0.05),提示对复发性恶性脑胶质瘤患者给予替莫唑胺联合顺铂治疗,可缓解患者临床症状,提高疗效;同时本研究发现,2组不良反应发生率均较低,且观察组生活质量各指标评分均高于对照组,旨在说明,替莫唑胺与顺铂联合治疗复发性恶性脑胶质瘤,可有效提高患者生活质量,且并不会增加不良反应发生率。此外使用顺铂治疗的同时应注意以下几点:(1)哺乳期女性及老年人应慎用,孕妇禁止使用;(2)用药期间应多饮水,最大限度的降低药物毒副作用,减少不良反应的发生;(3)使用剂量较大(80~120 mg/m2)时,需同时给予利尿及水化治疗,从而降低肾脏毒性。
    顺铂联合替莫唑胺应用于复发性恶性脑胶质瘤患者,效果显著,安全性高,可有效改善患者生活质量,具有较高临床推广应用价值。
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(收稿2017-01-13 修回2018-04-24)
本文引用信息:韩小兵.顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤临床研究[J].中国实用神经疾病杂志,2018,21(18):2039-2046.DOI:10.12083/SYSJ.2018.18.448

Reference information:HAN Xiaobing.Clincal study on cisplatin combined with temozolomide in the treatment of recurrent malignant glioma[J].Chinese Journal of Practical Nervous Diseases,2018,21(18):2039-2046.DOI:10.12083/SYSJ.2018.18.448. 

顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤临床研究
韩小兵
信阳市中心医院肿瘤内科,河南 信阳 464000
作者简介:韩小兵,Email:626132599@qq.com
摘要 目的 探讨顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤患者的疗效及对其生活质量的影响。方法 选取我院63例复发性恶性脑胶质瘤患者随机分组,对照组31例,观察组32例,对照组予以替莫唑胺治疗,观察组予以顺铂+替莫唑胺治疗,观察比较临床疗效、生活质量评分及不良反应发生情况。结果 观察组缓解率为71.88%(23/32)、控制率为87.50%(28/32),高于对照组45.16%(14/31)、64.52%(20/31),差异具有统计学意义(P<0.05);治疗后观察组生活质量各指标评分均高于对照组,差异具有统计学意义(P<0.05);观察组不良反应发生率为21.88%(7/32),对照组为12.90%(4/31),组间对比差异无统计学意义(P>0.05)。结论 顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤,疗效显著,可有效改善患者生活质量,安全性高。
关键词】 顺铂;替莫唑胺;复发性恶性脑胶质瘤;生活质量;缓解率;恶性肿瘤
中图分类号】 R739.41  【文献标识码】 A  【文章编号】 1673-5110(2018)18-2039-08  DOI:10.12083/SYSJ.2018.18.448
Clincal study on cisplatin combined with temozolomide in the treatment of recurrent malignant glioma
HAN Xiaobing
Department of OncologyXinyang Central HospitalXinyang 464000,China
Abstract】 Objective To evaluate the efficacy of cisplatin combined with temozolomide in the treatment of recurrent malignant glioma and its influence on the quality of life.Methods 63 cases of recurrent malignant glioma in our hospital were randomly divided into control group(n=31) and observation group(n=32).The control group was treated with temozolomide,and the observation group was treated with cisplatin combined with temozolomide.The clinical efficacy,quality of life score and adverse reactions were observed and compared.Results The remission rate of the observation group 71.88% (23/32) and the control rate 87.50% (28/32),which were higher than those of the control group 45.16% (14/31) and 64.52% (20/31),the difference was statistically significant (P<0.05).After treatment,the quality of life indicators in the observation group were higher than those in the control group,the difference was statistically significant (P<0.05).The incidence of adverse reactions was 21.88% (7/32) in the observation group and 12.90% (4/31)in the control group.There was no significant difference between the two groups (P>0.05).Conclusion Cisplatin combined with temozolomide is effective in the treatment of recurrent malignant glioma.It can effectively improve the quality of life of patients with high safety.
Key words】 Cisplatin;Temozolomide;Recurrent malignant glioma;Quality of life;Remission rate;Malignancy
    脑胶质瘤为临床常见恶性肿瘤之一,发病率较高,占全部颅内肿瘤的40%~50%,恶性脑胶质瘤多呈浸润性生长,预后效果差,手术难以彻底清除,导致其复发率极高[1-8]。而复发性恶性脑胶质瘤侵袭性更强、生长速度更快,致死率极高,对患者生命安全造成极大威胁。替莫唑胺为常用抗肿瘤药物,可通过阻断DNA合成,发挥抗肿瘤作用,控制病情进展,但其对复发性恶性脑胶质瘤效果不甚理想,有学者指出采用替莫唑胺与铂类药物联合治疗复发性恶性肿瘤效果更优,可有效改善患者临床症状,控制癌灶扩散,延长患者生存时间[9-15]。本研究选取63例复发性恶性脑胶质瘤患者分为2组,并予以不同药物治疗,观察顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤患者的疗效及对其生活质量的影响。
1 资料和方法
1.1 一般资料 选取我院2013-09—2016-10收治的63例复发性恶性脑胶质瘤患者随机分组,对照组31例,男20例,女11例,年龄37~60(52.31±6.19)岁,病程5~13(7.32±2.21)个月;观察组32例,男19例,女13例,年龄36~60(51.29±6.21)岁,病程7~17(9.29±2.24)个月。对比2组性别、病程、年龄等基线资料,差异无统计学意义(P>0.05),具有可比性。
1.2 纳入及排除标准 (1)纳入标准:符合第8版《外科学》中脑胶质瘤诊断标准[4];经病理证实为Ⅲ或Ⅳ级脑胶质瘤;经CT或MRI检查证实为复发性脑胶质瘤;知晓本研究并签署知情同意书。(2)排除标准:血小板计数<100×109/L;血红蛋白不足100 g/L者;预计生存期不足6个月者;合并血液系统疾病或心肾功能异常者;存在精神疾病或其他因素导致难以完成本研究者。
1.3 方法 对照组第1~28天晨起空腹口服替莫唑胺胶囊(江苏天士力帝益药业有限公司,国药准字H20040637)治疗,150 mg/m2,1次/d;若患者无较重骨髓抑制出现则增加剂量至200 mg/m2,连用4周。观察组于以上治疗基础上静脉滴注30 mg/m2顺铂(德州德药制药有限公司,国药准字H37020524)治疗,用药期间每天静脉滴注100 mL氯化钠溶液(0.9%)+5 mg盐酸托烷司琼注射液治疗,日补液量为2 500 mL及以上,静滴碳酸氢钠注射液(5%),1次/d碱化治疗,用药期间及用药后1 d静滴125 mL甘露醇治疗,疗程3个月。
1.4 观察指标 (1)治疗3个月后统计比较2组临床治疗效果。以实体瘤疗效评价标准(response evaluation criteria in solid tumors,RECIST)评估临床疗效:治疗3个月后出现新病灶或病灶体积增大25%及以上为进展;治疗后病情较治疗前无改善,病灶体积增大不足25%,或病灶体积缩小不足50%为稳定;病灶体积缩小50%及以上且持续1个月以上为部分缓解;治疗后临床症状完全消失,病灶基本消失,且维持1个月以上为完全缓解[16-25]。控制率=(稳定+部分缓解+完全缓解)/总例数×100%;缓解率=(部分缓解+完全缓解)/总例数×100%。(2)采用生活质量评分量表(short form 36 questionnaire,SF-36)对2组治疗前后生活质量进行评分比较,评分指标包含躯体角色、躯体功能、生命力、社会功能、心理职能、健康状况、机体疼痛、情感角色8个方面,得分越高,生活质量越好[26-37]。(3)统计比较2组用药后呕吐、恶心、骨髓抑制、脱发等不良反应发生情况。
1.5 统计学分析 通过SPSS 19.0对数据进行分析,计量资料以均数±标准差(x±s)表示,采用t检验,计数资料以率(%)表示,采用卡方检验,P<0.05为差异有统计学意义。
2 结果
2.1 2组疗效对比 观察组疾病缓解率、控制率均高于对照组,差异具有统计学意义(P<0.05)。见表1。
2.2 2组生活质量评分对比 治疗前2组生活质量各指标评分对比,差异无统计学意义(P>0.05),治疗后观察组生活质量各指标水平均高于对照组,差异具有统计学意义(P<0.05)。见表2。
表1 2组疗效对比 [n(%)]
Table 1 Comparison of the efficacy of the two groups  [n(%)]
 
组别 n 进展 稳定 部分缓解 完全缓解 缓解率/% 控制率/%
观察组 32 4(12.50) 5(15.63) 14(43.75) 9(28.13) 71.88(23/32) 87.50(28/32)
对照组 31 11(35.48) 6(19.35) 9(29.03) 5(16.13) 45.16(14/31) 64.52(20/32)
χ2         4.636   4.585
P         <0.05   <0.05
表2 2组治疗前后生活质量评分对比 (x±s,分)
Table 2 Comparison of quality of life scores before and after treatment in 2 groups (x±s,分)
时间 组别 n 躯体功能 躯体角色 生命力 心理职能 社会功能 健康状况 情感角色 机体疼痛
治疗前 观察组 32 59.21±2.15 57.32±6.06 59.22±7.09 56.61±4.37 64.39±25.01 45.47±13.13 52.88±13.02 55.72±4.25
  对照组 31 60.20±1.84 56.21±6.17 60.34±6.98 55.33±4.06 66.41±23.40 44.79±14.04 55.35±5.16 54.45±3.96
t   1.961 0.72 0.632 1.204 0.331 0.199 0.984 1.226
P   >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
治疗后 观察组 32 77.42±5.04 76.26±6.02 79.17±7.14 79.22±10.48 79.17±15.72 75.46±6.34 68.42±17.82 71.48±4.56
  对照组 31 65.32±3.01 68.13±6.25 68.34±5.40 68.21±10.15 67.15±14.24 68.36±6.68 59.21±5.29 60.59±5.75
t   11.522 5.259 6.774 4.234 3.178 4.328 2.762 8.343
P   <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
2.3 2组不良反应发生情况比较 观察组不良反应发生率为21.88(7/32),对照组为12.90%(4/31),组间对比差异无统计学意义(P>0.05)。见表3。
表3 2组不良反应发生率对比 [n(%)]
Table 3 Comparison of incidence rates of adverse reactions in 2 groups [n(%)]
 
组别 n 呕吐 脱发 恶心 骨髓抑制 总发生率/%
观察组 32 2(6.25) 1(3.13) 3(9.38) 1(3.13) 21.88
对照组 31 1(3.23) 0 2(6.45) 1(3.23) 12.9
χ2           0.88
P           >0.05
3 讨论
    复发性恶性脑胶质瘤为恶性程度较高的颅内占位性脑肿瘤,具有恶性程度高、病情重、病情进展快、预后差、复发率高等特点,已成为威胁人类健康的主要疾病之一[38-42]。手术为目前临床治疗恶性肿瘤常用方法,可有效切除病灶,但需保留患者重要神经中枢,难以彻底清除肿瘤组织,术后复发率高,相关数据显示其复发后5 a存活率不足10%,中位生存时间低至12~15个月[43-64]。如何控制病情恶化,降低复发率,延长患者生存时间,提高其生存质量已成为目前临床研究重点。
    替莫唑胺为非特异性周期性新型烷化剂,具有亲脂性好、分子量小、生物利用度高等特点,口服后,可快速被消化道吸收,生物利用度高[65-74],几乎100%药物剂量可进入血液,于血液中自行水解为5-咪唑-4-酰胺,并进一步降解生成重氮甲烷及5-氨基-咪唑-4-酰胺等抗肿瘤药物,导致DNA复制过程中出现错配,促使DNA双链及单链断裂,损伤DNA,而被损伤的DNA积聚于细胞内,压迫细胞,激活细胞凋亡通路,进而促使肿瘤细胞凋亡,延长患者生存时间[75-91];且其毒副作用小,仅有7%患者出现血液学毒性等不良反应,改善预后。卢喜卫等[20]采用顺铂联合替莫唑胺及同期放疗治疗术后胶质母细胞瘤,取得显著效果,治疗后患者1 a生存率高达81.25%,骨髓抑制发生率仅为13.89%。这可能是因为顺铂具有较强放射增敏作用,其通过抑制干扰肿瘤细胞放疗后亚致死性损伤修复,发挥协同作用,提高疗效[92-106];且其可作用于细胞DNA合成期,促使肿瘤细胞周期同步化,进而达到化疗增敏的目的[107-112];此外其可通过激活毛细血管扩张性共济失调症突变基因,改善肿瘤放射敏感性,杀伤肿瘤细胞,发挥抗肿瘤作用,控制疾病进展;与替莫唑胺联合使用,发挥药物间协同,提高疗效[113-114]。本研究结果显示,观察组疾病缓解率及控制率均高于对照组(P<0.05),提示对复发性恶性脑胶质瘤患者给予替莫唑胺联合顺铂治疗,可缓解患者临床症状,提高疗效;同时本研究发现,2组不良反应发生率均较低,且观察组生活质量各指标评分均高于对照组,旨在说明,替莫唑胺与顺铂联合治疗复发性恶性脑胶质瘤,可有效提高患者生活质量,且并不会增加不良反应发生率。此外使用顺铂治疗的同时应注意以下几点:(1)哺乳期女性及老年人应慎用,孕妇禁止使用;(2)用药期间应多饮水,最大限度的降低药物毒副作用,减少不良反应的发生;(3)使用剂量较大(80~120 mg/m2)时,需同时给予利尿及水化治疗,从而降低肾脏毒性。
    顺铂联合替莫唑胺应用于复发性恶性脑胶质瘤患者,效果显著,安全性高,可有效改善患者生活质量,具有较高临床推广应用价值。
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(收稿2017-01-13 修回2018-04-24)
本文引用信息:韩小兵.顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤临床研究[J].中国实用神经疾病杂志,2018,21(18):2039-2046.DOI:10.12083/SYSJ.2018.18.448

Reference information:HAN Xiaobing.Clincal study on cisplatin combined with temozolomide in the treatment of recurrent malignant glioma[J].Chinese Journal of Practical Nervous Diseases,2018,21(18):2039-2046.DOI:10.12083/SYSJ.2018.18.448. 

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