体外药敏实验及MGMT表达为依据的恶性脑胶质瘤个体化化疗:42例近期疗效分析  

Individualized Chemotherapy Based on Drug Sensitivity and Resistance Assay and MGMT Protein Expression for Patients with Malignant Glioma——Analysis of 42 Cases

作　　者：张俊平[1] 史鸿浏[1] 赛克[1] 岳伟英[1] 牟永告[1] 张湘衡[1] 陈忠平[1] 

机构地区：[1]华南肿瘤学国家重点实验室

出　　处：《癌症》2006年第12期1533-1537,共5页Chinese Journal of Cancer

基　　金：广东省自然科学基金(No.5300799);卫生部基金项目(No.W200501033)~~

摘　　要：背景与目的:脑胶质瘤细胞对化疗药物耐药是导致化疗有效率低的重要原因之一。O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNAmethyltransferase,MGMT)可使DNA烷基化损伤得到修复,是细胞对治疗恶性脑胶质瘤的常用药物亚硝脲类及替莫唑胺(temozolomide,TMZ)产生耐药的主要原因。本研究采用体外药敏实验和检测肿瘤MGMT表达指导进行恶性脑胶质瘤个体化化疗,评价其近期疗效和不良反应。方法:经手术后病理确诊的恶性脑胶质瘤患者42例,取其新鲜肿瘤组织采用MTT法进行体外药敏实验,免疫组织化学方法检测肿瘤组织MGMT蛋白表达,根据体外药敏实验及MGMT测定结果选择化疗方案进行化疗。42例患者中有7例接受了2个方案化疗,共49例次可评价近期疗效。按WHO疗效评价标准进行近期疗效评价。不良反应评价按照美国国立癌症研究所评价标准。结果:6例次(12%)完全缓解,10例次(20%)部分缓解,20例次(41%)稳定,13例次(27%)进展。客观有效率为33%,疾病控制率为73%。80个周期可以评价不良反应,化疗的主要剂量限制性毒性为骨髓抑制,Ⅲ、Ⅳ级中性粒细胞减少占28%(22/80),Ⅳ级血红蛋白降低占1%(1/80),Ⅲ、Ⅳ级血小板减少占8%(6/80)。非血液学毒性主要为恶心/呕吐、脱发和疲劳。结论:根据体外药敏实验及MGMT蛋白表达选择化疗方案,对恶性脑胶质瘤患者进行个体化化疗,可以提高近期化疗疗效。BACKGROUND ＆ OBJECTIVE： Malignant glioma cells are resistant to most chemotherapeutic agents. Nitrosourea and temozolomide （TMZ） are main agents for treating malignant glioma. Resistance of malignant glioma to these agents is frequently associated with high levels of DNA repair protein O^6-methylguanine-DNA methyltransferase （MGMT）. This study was to evaluate the efficacy of individualized chemotherapy, according to chemotherapy sensitivity and resistance assays （CSRAs） and MGMT expression pattern, on malignant glioma, and observe the adverse events. METHODS： The pathologically confirmed malignant glioma patients, treated by operation at Cancer Center of Sun Yat-sen University from Dec. 2001 to Feb. 2006, were enrolled. The fresh tumor tissues obtained during operation were immediately sent for CSRAs using MTT assay. The expression of MGMT： protein was detected by immunohistochemistry. After radiotherapy,the patients received chemotherapy according to the results of CSRAs and MGMT expression. The patients were evaluated for response to chemotherapy according to WHO criteria, and for toxicity according to National Cancer Institute （NCI） criteria. RESULTS： Forty-two patients were evaluated for response to chemotherapy. Seven patients received 2 chemotherapy regimens consecutively, therefore, overall 49 cases were evaluable. Of the 49 cases, 6（12%） achieved complete remission （CR）, 10 （20%） achieved partial remission （PR）, 20 （41%） had stable disease （SD）, and 13 （27%） had progressive disease （PD）. The objective response rate （CR and PR） was 33%, and the disease control rate （CR, PR, and SD） was 73%. Hematologic toxicities were the main adverse events observed in this study, included grade IV anemia （1%）, grade Ⅲ-Ⅳ leukopenia （28%）, and grade Ⅲ -Ⅳ thrombocytopenia （8%）. Non-hematologic toxicities mainly included nausea/vomit, fatigue, and alopecia. CONCLUSION ： Individualized chemotherapy based on in vitro CSRAs and MGMT express

关 键 词：脑肿瘤 胶质瘤 体外药敏实验 MGMT 化学疗法 个体化 

分 类 号：R739.4[医药卫生—肿瘤] R730.53[医药卫生—临床医学]