Stereotactic radiosurgery for atypical and anaplastic meningiomas

Convection-enhanced delivery (CED) is a local infusion technique, which delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood–brain barrier and reducing systemic side effects. CED distribution is significantly increased if the infusate is hydrophilic. This study evaluated the safety and efficacy of CED of nimustine hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), a hydrophilic nitrosourea, in rat 9 l brain tumor models. The local neurotoxicity of ACNU delivered via CED was examined in normal rat brains, and the maximum tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD produced significantly longer survival time than systemic administration (P < 0.05, log-rank test). Long-term survival (80 days) and eradication of the tumor occurred only in the CED-treated rats. The tissue concentration of ACNU was measured by high-performance liquid chromatography, which revealed that CED of ACNU at the dose of 100-fold less total drug than intravenous injection carried almost equivalent concentrations of ACNU into rat brain tissue. CED of hydrophilic ACNU is a promising strategy for treating brain tumors.     

尼莫司汀联合多西他赛治疗肺癌脑转移瘤的疗效观察

目的研究尼莫司汀联合多西他赛治疗肺癌脑转移瘤的疗效。方法收集2009年1月-2012年12月肺癌出现脑转移患者32例,将患者随机分为治疗组17例和对照组15例,治疗组用尼莫司汀联合多西他赛进行治疗,对照组单用尼莫司汀治疗。观察2组近期疗效和不良反应发生情况。结果治疗组总有效率高于对照组,头痛、乏力和恶心呕吐程度轻于对照组,差异均有统计学意义(P<0.05,P<0.01)。结论尼莫司汀联合多西他赛治疗肺癌脑转移瘤有较好的疗效,安全性好,且未见严重不良反应。     

Multicenter randomized study on Me-CCNU, 5-FU and ADM vs ACNU, 5-FU and ADM for treatment of advanced gastric cancer

AIM: To compare the efficacy of a combined chemotherapy regimen of 5-fluouracil (5-FU) and adriamycin (ADM) with nimustine hydrochloride (ACNU; brand name Nidran), a new nitrosourea agent, or with methyl-CCNU for advanced gastric cancer.METHODS: One-hundred-and-three cases of advanced gastric cancer were randomly allocated into Group A (Me-CCNU, 5-FU and ADM combination) and Group B (ACNU, 5-FU and ADM combination). The quality of life (QOL) questionnaire, composed of 11 ordinal categorical items, was used to collect data from these patients.RESULTS: Group A had no case of complete remission (CR) or partial remission (PR), while Group B had no CR but 8 PR (8/46 cases), for a response rate of 0% in Group A and 17.4% in Group B. The median survival time in Group A was 108 d and in Group B was 112 d. Both groups tolerated the treatment well and there were no serious adverse effects. QOL evaluations showed better psychological and physical feelings of tiredness for Group B than for Group A, and scores based on facial scaling showed a more pleasant inclination for the former.CONCLUSION: ACNU combination is superior to the Me-CCNU combination for advanced gastric cancer patients.     

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。     

ACNU-based chemotherapy for recurrent glioma in the temozolomide era

No standard of care for patients with recurrent glioblastoma has been defined since temozolomide has become the treatment of choice for patients with newly diagnosed glioblastoma. This has renewed interest in the use of nitrosourea-based regimens for patients with progressive or recurrent disease. The most commonly used regimens are carmustine (BCNU) monotherapy or lomustine (CCNU) combined with procarbazine and vincristine (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n = 14) or in combination with other agents (n = 18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide.     

ACNU与 Vm-26合用治疗脑瘤的实验研究

目的：观察尼莫司汀（nimustine,ACNU)与威猛（teniposide,Vm-26）合用对脑瘤的增效作用。方法：体外采用MTT法比较ACNU、Vm-26单用与两者合用对人脑胶质母细胞瘤株生长的抑制作用，动物实验以小鼠移植性脑瘤（G422）的皮下接种型及脑内接种型为材料，分别观察ACNU和Vm-26单用与合用对两个动物模型的抑制作用，皮下接种型比较瘤块大小，脑内接种型则以生存时间为标准。结果：体内试验，脑瘤皮下接种型中单用ACNU、Vm-26的抑瘤率分别为56．5％及82．8％，两者合用后达99．1％，且该组12只动物中有9只不出现肿瘤，脑瘤脑内接种型的结果为ACNU、Vm-26单用生存率延长分别为7．7％及6．7％，而合用组为35．4％，体外试验显示Vm-26(0.01或1μg/μl）分别与ACNU1、4及8μg/μl合用有明显协同作用，同样ACNU（0．5、2μg/μl）分别与Vm-26(0．01、0．1或0．25μg/μl）合用亦增效。以IC50为指标，ACNU2或6μg/μl与Vm-26合用增强倍数分别为2及12倍。结论：体内外抗脑瘤试验的结果均显示ACNU与Vm-26合用较两药单用时有显著增效作用。     

嘧啶亚硝脲对胶质母细胞瘤A-172细胞中Bcl-xL mRNA和蛋白表达的影响

目的 探讨嘧啶亚硝脲(ACNU)对人胶质母细胞瘤A-172细胞Bcl-xL mRNA及其蛋白表达和A-172细胞增殖活性的影响.方法用免疫组化SP法、RT-PCR和MTT法分别检测不同浓度ACNU作用于A-172细胞后Bcl-xL mRNA、蛋白的表达.结果不同浓度ACNU作用A-172细胞后Bcl-xL mRNA相对水平均高于未加ACNU作用的A-172细胞(P<0.01),随着ACNU浓度的增加,Bcl-xL蛋白表达逐渐下降,对细胞增殖活性的抑制率逐渐增高;ACNU为25μg/ml时,细胞增殖抑制率增幅最大为54.48%.结论 A-172细胞中Bcl-xL mRNA、蛋白呈高表达.ACNU可以诱导降低胶质母细胞瘤A-172细胞中Bcl-xL的表达,促进其细胞凋亡.对A-172细胞增殖活性具有明显抑制作用.     

RP-HPLC测定小鼠脑匀浆中的盐酸尼莫司汀

目的 采用HPLC法测定小鼠脑匀浆中的盐酸尼莫司汀.方法 使用Diamonsil C_(18)柱,流动相为甲醇-水-三乙胺(20:79.5:0.5,磷酸调pH3),流速1.0 mL·min~(-1),检测波长241 nm,柱温35℃.结果 盐酸尼莫司汀0.20～5.00 mg·L~(-1)与峰面积的线性关系良好(r=0.9999);平均方法回收率95.7%,平均萃取回收率101.2%,日内、日间RSD均<5%.结论 该方法简便、灵敏、准确,可用于测定脑匀浆中的盐酸尼莫司汀.     

替尼泊苷与尼莫司汀联合方案治疗肺癌脑转移瘤近期疗效分析

背景与目的：脑转移瘤的原发肿瘤以肺癌最为常见，肺癌脑转移瘤患者治疗效果并不理想。本研究应用替尼泊苷（VM-26）和尼莫司汀（ACNU）联合方案治疗肺癌脑转移瘤患者，观察其对肺癌脑转移瘤的临床治疗效果，评价其不良反应。方法：2006年12月至2008年5月，中国抗痛协会神经肿瘤专业委员会组织全国15家单位对经手术或病理活检确诊的肺癌脑转移瘤患者，应用VM-26与ACNU联合方案化疗，观察近期疗效。化疗方案为VM-26，每天80～100mg／m^2，d1-3；6-8周重复一次；ACNU，2-3mg／kg，d1，6-8周重复一次。结果：278例患者资料完整、可行近期疗效评价，上述病例共行897周期化疗，平均3．2个周期。全组无完全缓解（complete response，CR）病例，77例（27．7％）部分缓解（partial response，PR），139例（50％）稳定（stable disease，SD），62例（22.3％）进展（progressive disease，PD）。客观有效率（CR＋PR）为27．7％，疾病控制率（CR＋PR＋SD）为77．7％。化疗的主要剂量限制性毒性为骨髓抑制，Ⅲ、Ⅳ度中性粒细胞减少症发生率分别为23．1％（207／897）；20.1％（180／897），Ⅲ、Ⅳ级血小板减少症发生率分别为19．6％（176／897）、14．5％（130／897）。按既往是否接受化疗，患者可分为既往接受化疗组、未接受化疗组，前者较之后者，Ⅳ度中性粒细胞减少症、Ⅳ度血小板减少症、Ⅲ及Ⅳ度中性粒细胞减少症、Ⅲ度及Ⅳ度血小板减少症发生率均明显升高（P均〈0．05）。结论：VM-26与ACNU联合方案主要毒性为Ⅲ、Ⅳ度骨髓抑制，在既往行化疗患者发生率较高，但可控制。该方案治疗肺癌脑转移瘤，客观有效率与其它常用方案相似、疾病控制率较高。     

注射用盐酸尼莫司汀的稳定性考察

目的:考察不同温度、光照及pH值条件下注射用盐酸尼莫司汀(ACNU)与0.9%氯化钠注射液配伍的稳定性,为临床合理用药提供依据。方法:采用高效液相色谱法测定其主药含量,并观察配伍液的外观、pH值等变化。结果:ACNU检测浓度的线性范围为10～100μg.mL-1(r=0.9998);平均回收率为99.81%(RSD=0.68%);温度、光照及0.9%氯化钠注射液pH值3种因素均对ACNU稳定性有影响。结论:临床应用ACNU时应现配现用,且配伍后溶液冷藏、避光贮存不超过8h。