恶性星形细胞瘤采用尼莫司汀、替尼泊苷联合化疗的疗效分析

目的 探讨尼莫司汀、替尼泊苷联合治疗恶性星形细胞瘤的疗效.方法 对31例经病理诊断明确的恶性星形细胞瘤采用手术和放疗后采用尼莫司汀、替尼泊苷联合化疗的病例进行随访,同时将22例仪接受手术加放疗的恶性星形细胞瘤病例作为对照组.化疗采用尼莫司汀(宁得朗)2～3mg/kg,每疗程静脉给药1次,替尼泊苷300mg/m2,分成5d静脉给药,每6周为1个疗程,定期随访病人,采用Kaplan-Meier法统计随访结果 .结果 对照组的中位无进展生存时间为11.5个月,综合治疗组的中位无进展生存时间为13.5个月,综合治疗组病人中位无进展生存时间提高2个月.结论 尼莫司汀和替尼泊苷联合化疗方案对于恶性星形细胞瘤的治疗有一定疗效.     

调强适形放疗和序贯化疗治疗脑胶质瘤

我们自2001年1月至2004年6月,采用调强适形放射治疗(intensity modulated radiotherapy,IMRT)序贯尼莫司汀(nimustine,ACNU)和替尼泊苷(teniposide,VM-26)联合化疗治疗28例恶性胶质瘤.分析报告如下.     

Ommaya囊置入及囊内化疗治疗颅内囊性胶质瘤的临床应用研究

目的探讨Ommaya囊置入术及尼莫司汀(nimustine,ACNU)囊内化疗对颅内囊性胶质瘤的治疗效果。方法对诊断明确的31例颅内囊性胶质瘤患者,置入Ommaya囊后,再进行穿刺引流囊液和Ommaya囊内注射尼莫司汀。结果 18例恶性程度高的胶质瘤近期(2～3个月)随访结果:临床症状消失11例,好转4例,死亡3例。13例低度恶性胶质瘤中远期(6～42个月)随访结果:临床症状消失9例,好转2例,加重1例,死亡1例。结论本组结果表明立体定向置入Ommaya囊结合尼莫司汀囊内化疗是临床治疗颅内囊性胶质瘤一种简便、经济、有效、创伤小的好方法。     

原代胶质瘤细胞化疗药物敏感性研究

目的 观察不同抗肿瘤药物在体外对原代人胶质瘤细胞的敏感性,为临床筛选化疗药物、制订个体化方案提供指导.方法 46例经手术后病理证实的胶质瘤新鲜组织标本进行体外原代培养,流式细胞术Annexin V-FITC/PI双染法榆测替尼泊苷、尼莫司汀、甲氨蝶呤和替莫唑胺在体外对原代胶质瘤细胞的敏感性;分析不同化疗药物敏感性与患者性别、年龄和肿瘤病理分级之间的关系.结果 人胶质瘤细胞对4种化疗药物敏感性的强弱程度依次为替尼泊苷(39.13%)、替莫唑胺(34.78%)、尼莫司汀(26.09%)和甲氨蝶呤(6.52%),组间差异具有统计学意义(x2=14.770,P=0.002);甲氨蝶呤组患者对化疗药物敏感性最低,与其他各组比较差异有统计学意义(x2=13.883,11.210,6.452;均P＜0.05).亚组分析提示,性别和年龄对化疗药物敏感性无显著影响(均P＞0.05),但不同WHO病理分级对替莫唑胺化疗敏感性存在差异并具有统计学意义(x2=4.305,P=0.038).结论 不同胶质瘤个体对化疗药物的敏感性不同,以替尼泊苷抗胶质瘤作用较强,替莫唑胺对高级别胶质瘤药物化疗效果更佳.流式细胞术可作为快速化疗药物敏感性检测方法,为胶质瘤筛选化疗药物并制订个体化方案.     

脑胶质瘤细胞体外原代培养化疗药物敏感性研究

目的探讨脑胶质瘤原代培养细胞对常用化疗药物的敏感性,为临床脑胶质瘤切除术后病人进行最佳的个体化化疗提供理论依据。方法取手术切除的80例人脑恶性胶质瘤的新鲜临床标本进行原代培养,采用MTT法检测恶性脑胶质瘤细胞对长春新碱(VCR)、顺铂(DDP)、尼莫司汀(ACNU)、替莫唑胺(TMZ)、替尼泊甙(VM-26)的体外敏感性。结果长春新碱(VCR)、顺铂(DDP)、尼莫司汀(ACNU)、替莫唑胺(TMZ)、替尼泊甙(VM-26)的敏感率分别为9.4%、43.8%、57.8%、51.6%和62.5%,VM-26的敏感率最高,差异有统计学意义(P<0.05)。结论用MTT法进行化疗药物的敏感性测定可以指导临床个体化化疗方案的制定,避免耐药药物的盲目应用。     

高压氧对脑内种植GL261胶质瘤C57小鼠尼莫司汀化疗后生存期的影响

目的观察高压氧辅助治疗对脑内种植GL261胶质瘤细胞系C57小鼠尼莫司汀(嘧啶亚硝脲)化疗后平均生存期的影响。方法于C57小鼠右侧尾状核种植GL261胶质瘤细胞,术后第7天分别接受单纯高压氧或单次尼莫司汀化疗或高压氧与尼莫司汀联合治疗,观察不同治疗方法对荷瘤鼠生存期的影响。结果大体标本观察显示,不同处理组荷瘤鼠肿瘤体积均较大、占位效应明显,正常脑组织受压严重、中线结构偏移,但不同处理组肿瘤体积比较差异无统计学意义(F=0.602,P=0.618)。平均生存期(F=12.177,P=0.000)评价和Kaplan-Meier生存曲线分析(χ2=13.604,P=0.003)显示,单纯高压氧治疗(χ2=0.365,P=0.546)和单次尼莫司汀化疗(χ2=0.884,P=0.347)对荷瘤鼠生存期无明显影响;高压氧联合尼莫司汀化疗(χ2=9.962,P=0.002)可延长荷瘤鼠生存时间,且疗效优于单纯高压氧治疗(χ2=6.925,P=0.008)和单次尼莫司汀化疗(χ2=7.152,P=0.007)。结论高压氧对颅内种植GL261胶质瘤细胞系的C57小鼠生存期和生长无明显影响和促进作用,联合尼莫司汀化疗则可使荷瘤鼠平均生存期明显延长,提示高压氧对尼莫司汀化疗具有增效作用。     

替尼泊甙联合司莫司汀治疗脑胶质瘤疗效与MGMT表达关系的研究

目的 通过观察脑胶质瘤中O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)的表达状态,探讨MGMT在脑胶质瘤中的表达与替尼泊甙(VM-26)联合司莫司汀(Me-CCNU)方案化疗疗效之间的关系. 方法 对资料完整的47例经病理证实的脑胶质瘤患者进行回顾性研究,对患者的胶质瘤病理石蜡切片采用免疫组化法检测MGMT的表达,然后分析MGMT的表达与患者生存率之间关系. 结果 本组患者MGMT阳性表达率为40.4%.MGMT阴性表达组3年生存率为66.7%,平均总生存时间为(67.861±10.094)月;MGMT阳性表达组为52.6%,平均总生存时间为(47.263±7.983)月,比较差异均无统计学意义(P>0.05).11例患者出现I度的骨髓抑制现象,6例患者出现胃部不适、呕吐、腹泻、食欲不振等消化系统症状. 结论 VM-26联合Me-CCNU化疗方案可以有效克服脑胶质瘤中MGMT所带来的化疗耐药性问题,且该方案的毒副作用不大,是一个有效的化疗方案.     

58例脑恶性胶质瘤术后放化疗疗效临床观察

目的 观察脑恶性胶质瘤术后同步选择性动脉灌注尼莫司汀(ACNU)联合三维适形放疗与单纯三维适形放疗的疗效、生存率及安全性比较.方法 治疗组为脑恶性胶质瘤28例经开颅显微手术后同步选择性动脉灌注ACNU联合三维适形放疗;对照组为脑恶性胶质瘤30例术后单纯二维适形放疗.结果 同步放化疗组脑恶性胶质瘤治疗CR、PR高丁对照组(P<0.05),生存期也长于对照绢(P<0.05),其不良反应小、生存质量明显提高.结论 显微手术后同步选择性动脉灌注ACNU联合适形放疗治疗脑恶性胶质瘤疗效较好,有望成为目前脑恶件胶质瘤的常规治疗方案之一.     

脑恶性胶质瘤经动脉超选化疗的初步观察

目的观察脑恶性胶质瘤采用尼莫司汀经动脉超选化疗的疗效及安全性。方法回顾性分析64例脑恶性胶质瘤病人的临床资料,其中多形性胶质母细胞瘤38例,间变性星形细胞瘤22例,胶质肉瘤4例。显微镜下尽量切除肿瘤,术后采用尼莫司汀(2.5 mg/kg)行经动脉超选化疗。结果肿瘤全切除56例,大部分切除6例,部分切除2例。所有病例随访3～18个月,平均8个月。术后复发8例(12.50%),其中再次手术2例。化疗前后KPS评分差异无统计学意义(P>0.05)。出现不同程度骨髓抑制40例(62.50%);胃肠道反应4例(6.25%);未见与介入操作相关的并发症、肝肾功能改变、眼部及神经系统并发症。结论脑恶性胶质瘤采用尼莫司汀经动脉超选化疗是一种安全、有效的辅助治疗方法,值得进一步研究。     

经颈动脉灌注ACNU、VM-26联合治疗复发性脑胶质瘤的临床研究

目的研究经颈动脉灌注盐酸尼莫司汀（ACNU）和替尼泊苷（VM-26）联合治疗复发性脑胶质瘤的效果及相关问题。方法治疗组选择幕上颈内动脉供血范围的复发性脑胶质瘤164例，肿瘤同侧颈总动脉ACNU和VM-26联合灌注化疗。对照组选择复发性脑胶质瘤26例，口服司莫司汀治疗，并行疗效对比。结果治疗组完全缓解率和部分缓解率明显高于对照组（P〈0．05），恶化率明显低于对照组（P〈0.05），生存期明显长于对照组（P〈0.05）。结论经颈动脉灌注ACNU、VM-26治疗复发性脑胶质瘤疗效好，副作用小，安全可靠，可作为常规化疗手段。     

MGMT表达指导下的恶性脑胶质瘤预见性化疗近期疗效分析

目的评价根据O~6-甲基鸟嘌呤-DNA甲基转移酶(O~6-methylguanine-DNA methyhransferase,MGMT)表达指导的恶性脑胶质瘤化疗的近期疗效和毒副反应。方法经手术后病理确诊的恶性脑胶质瘤患者28例,用免疫组织化学方法检测肿瘤组织MGMT蛋白表达,对MGMT表达阳性者采用不含亚硝脲类和替莫唑胺的方案进行化疗,MGMT表达阴性者用药不受限。按WHO疗效评价标准评价近期疗效。不良反应评价按美国国立癌症研究所评价标准。结果28例中有4例进行了两个方案化疗,共32化疗例次进入疗效评价。5例次完全缓解(complete response,CR),6例次部分缓解(partial response,PR),12例次稳定(stable disease,sD),9例次进展(progressive disease,PD)。客观有效率(CR PR)为35%,疾病控制率(CR PR SD)为73%。化疗的主要剂量限制性毒性为骨髓抑制。非血液学毒性主要为恶心呕吐和脱发。结论对恶性脑胶质瘤病人在化疗之前检测MGMT蛋白表达,指导选择化疗方案,可以明显提高近期化疗疗效(有效率35%,传统亚硝脲类药物对恶性胶质瘤的有效率仅20%),毒副反应耐受性好。     

Treatment of supratentorial glioma in adults by intra-arterial HECNU. Experience of the Pitié-Salpétrière group]

Between 1984 and 1988, patients suffering from malignant gliomas received intraarterial chemotherapy with HECNU (IAC). Three groups were identified. Group 1 consisted of 56 patients previously treated with surgery and radiation therapy (RT), who received IAC at recurrence. Group 2 consisted of 46 patients with unresectable tumors, and group 3 of 40 patients who had their tumor surgically removed. In groups 2 and 3, three courses of IAC were administered prior to conventional RT (50-54 Gy). Immediate tolerance was good but delayed ocular and cerebral toxicity occurred in 14% and 11% of cases, respectively. A better therapeutic response was observed with anaplastic gliomas than with glioblastomas (GBM). For anaplastic gliomas, median survivals (MS) were 18 months (group 1), 24 months (group 2) and 30 months (group 3). For GBM, MS were 4.5, 7.5 and 10.5 months in groups 1, 2 and 3, respectively. IAC does not seem to improve the prognosis of GBM.     

3D conformal radiotherapy and cisplatin for recurrent malignant glioma

PURPOSE: To determine the maximum tolerated dose of 3D conformal radiotherapy in combination with Cisplatin for patients with recurrent malignant gliomas. METHODS: From 1999-2003, nine patients with recurrent malignant glioma received fractionated radiotherapy and Cisplatin (20 mg/m2/d IV on days 1-5) in a Phase I radiation dose escalation trial. Three sequential dose levels were evaluated: 25 Gy, 30 Gy, and 35 Gy, using 5 Gy fractions. All patients received prior external beam radiation (median dose 59.4 (20-60) Gy) and five patients received prior chemotherapy. RESULTS: Six male and three female patients were enrolled with a median age of 52 years, and a median Karnofsky performance status score of 70. The median re-irradiated tumor volume was 18.9 (0.1-78.5) cm3 and the median follow-up was 8.8 (3.2-31.2) months. One patient (30 Gy/ 6 fractions) experienced medically reversible acute grade 3 toxicity. A second patient (35 Gy/ 7 fractions) experienced acute grade 2 toxicity and histology showed tumor and radiation effect. A third patient (25 Gy/ 5 fractions) experienced late grade 3 toxicity from radiation necrosis. The radiological responses consisted of complete response (1 patient), partial response (1 patient), and stable disease (2 patients). The median overall survival was 8.8 months (95% CI 8.0-9.9), and the median disease free interval was 2.0 months (95% CI 1.4-4.4). Seven patients received chemotherapy following re-irradiation and Cisplatin. CONCLUSION: The maximum tolerated dose of 3D conformal fractionated radiotherapy was 30 Gy in 6 fractions with low dose Cisplatin, which was well tolerated in terms of acute toxicity for our patient population. This regimen demonstrated only modest efficacy in the treatment of recurrent malignant glioma. Combinations of conformal re-irradiation and other systemic agents may merit investigation. Currently our recommended dose is 30 Gy in 6 fractions for selected patients.     

脑胶质瘤术后超选介入化疗联合放疗临床分析

目的探讨脑胶质细胞瘤术后,应用超选介入化疗联合放疗消除或抑制残存肿瘤细胞的疗效。方法2001年5月至2005年1月,对38例脑胶质细胞瘤进行全切或大部切除术后,术后第2w开始应用化疗药物盐酸尼莫司汀(ACNU)超选介入化疗,采用Seldinger技术,微导管置入超过眼动脉,用生理盐水50ml稀释ACNU后,微泵调控注射1h,每周一次,4次为一疗程,6w后第2疗程,第一疗程后行全脑放疗(总量50~60Gy)。结果平均随访2.3年,38例中,显效12例:肿瘤完全消失(CR),有效18例:部分消失(PR,肿瘤减小50%以上),微变化(MR,肿瘤减小25%)及无变化(NC)6例,恶化(PD)2例。总有效率78.9%。手术 超选介入化疗 放疗(OIR)组与手术 系统化疗 放疗(OSR)组比较预后差别显著(P<0.01)。结论OIR治疗脑胶质细胞瘤有明显疗效。     

Effectiveness of spray application of ACNU in the local control of malignant gliomas: report of two cases

Malignant gliomas encompassing the eloquent areas cannot be removed totally and their surgical extirpation is followed by adjuvant therapy for the residual tumor. Recently, we have employed fibrin glue as a vehicle for the sustained release of ACNU (nimustine hydrochloride) by spray application following subtotal tumor removal in two patients with recurrent malignant gliomas. Follow-up MRI at six months demonstrated no neuroradiological evidence of tumor recurrence in the site of operation. We conclude, this novel mode of intra-operative local chemotherapy by spray application of fibrin glue containing antineoplastic agent is effective in the control of residual tumor progression and may also prevent local recurrence and hence suggests its possible role as an adjuvant therapy in the management of malignant gliomas.     

Effectiveness of spray application of ACNU in the local control of malignant gliomas: Report of two cases

Abstract

Malignant gliomas encompassing the eloquent areas cannot be removed totally and their surgical extirpation is followed by adjuvant therapy for the residual tumor. Recently, we have employed fibrin glue as a vehicle for the sustained release of ACNU (nimustine hydrochloride) by spray application following subtotal tumor removal in two patients with recurrent malignant gliomas. Follow-up MRI at six months demonstrated no neuroradiological evidence of tumor recurrence in the site of operation. We conclude, this novel mode of Intra-operative local chemotherapy by spray application of fibrin glue containing antineoplastic agent is effective in the control of residual tumor progression and may also prevent local recurrence and hence suggests its possible role as an adjuvant therapy in the management of malignant gliomas. [Neurol Res 2000; 22: 181-184]     

Chemotherapy for malignant gliomas based on histoculture drug response assay : a pilot study

Objective

The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials.

Methods

Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image.

Results

Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months (p=0.07).

Conclusion

HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.     

立体定向植入缓释型5-Fu治疗恶性复发脑胶质瘤

目的探讨立体定向植入5-氟尿嘧啶多聚缓释体(缓释型5-FU)在治疗恶性脑胶质瘤中的作用。方法 2004年2月至2006年12月,将45例经手术切除后组织细胞学确诊、且术后复发的恶性胶质瘤患者分成两组:A组25例复发胶质瘤(采取患者自愿原则),行立体定向术植入缓释型5-Fu粒子肿瘤间质内化疗,同时配合直线粒子加速器外放疗。B组20例复发胶质瘤,采用直线粒子加速器外放疗为对照组。观察客观疗效,临床受益反应,毒性反应,并发症及生存情况。结果随访时间6~36个月。A组随访17例,B组随访13例。6和12个月累积生存率两组为53.0%比35.6%和20.5%比12.5%(P<0.05)。中位生存时间两组为8.2比4.1个月。平均生存时间两组为8.7比5.0个月(P<0.05)。结论立体定向植入缓释型5-Fu治疗脑恶性胶质瘤有疗效肯定,可延长患者生存,提高生存质量,无明显毒副作用,是一种安全有效的治疗方法。     

高级别脑胶质瘤患者术后同步放化疗的临床疗效研究

目的探讨术后不同方案同步放化疗和单纯放疗对高级别脑胶质瘤患者的疗效和安全性的差异。 方法海军总医院放射肿瘤科自2004年6月至2008年6月间采用不同方案治疗经病理证实的高级别脑胶质瘤患者59例,均行三维适形放射治疗(3D-CRT),其中联合替莫唑胺(TMZ)化疗患者21例（A组,Ⅲ级13例,Ⅳ级8例）,联合尼莫司汀(ACNU)加替尼泊苷(VM-26)化疗患者26例（B组,Ⅲ级14例、Ⅳ级12例）,未联合化疗患者12例（C组,Ⅲ级8例,Ⅳ级4例）。分析比较3组患者的疗效、不良反应和生存率。 结果A、B组患者的治疗有效率均高于C组,差异有统计学意义(P＜0.05);B组血液学毒性、消化道副反应的发生率较A组高,差异均有统计学意义(P＜0.05);全组中位疾病无进展生存时间(PFS)为8个月,中位总生存时间(OS)为15个月,Log-rank检验结果显示3组患者疾病无进展生存率、生存率不同,差异有统计学意义（P＜0.05）,A、B组患者的疾病无进展生存率、生存率均高于C组,差异有统计学意义(P＜0.05)。 结论高级别脑胶质瘤患者术后同步放化疗效果显著优于单纯放疗,可提高肿瘤治疗有效率及患者的PFS和OS。化疗方案推荐使用TMZ单药化疗,其与ACNU加VM26联合化疗疗效相当,但毒副反应更低。