MGMT表达指导下的恶性脑胶质瘤预见性化疗近期疗效分析  

Predictive chemotherapy according to O^6-methylguanine-DNA methyltransferase protein expression for malignant gliomas

作　　者：张俊平[1] 牟永告[1] 张湘衡[1] 赛克[1] 吴秋良[2] 岳伟英[1] 陈忠平[1] 

机构地区：[1]华南肿瘤学国家重点实验室,中山大学肿瘤医院神经外科,神经肿瘤科,广州510060 [2]华南肿瘤学国家重点实验室,中山大学肿瘤医院病理外科,广州510060

出　　处：《中华神经外科杂志》2007年第2期96-98,共3页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金资助项目（30271329）;华南肿瘤学国家重点实验室985-Ⅱ基金资助项目（31722）;广东省自然科学基金资助项目（5300799）

摘　　要：目的 评价根据O^6-甲基鸟嘌呤-DNA甲基转移酶（O^6-methylguanine-DNAmethyltransferase，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（completeresponse，CR），6例次部分缓解（partialresponse，PR），12例次稳定（stabledisease，SD），9例次进展（progressivedisease，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。Objective To evaluate the response to predictable chemotherapy according to O^6- methylguanine-DNA methyltransferase （MGMT） expression pattern and toxicity in patients with malignant gliomas. Methods Twenty-eight patients with histologically confirmed malignant gliomas were enrolled in this study. The glioma tissues were examined for MGMT protein expression by immunohistochemistry. The chemotherapeutic regimen did not consist of nitrosourea or temozolomide in patients with MGMT positive tumors, while no limitation for using nitrosourea or temozolomide in patients with MGMT negative tumors. The patients were evaluated for response to therapy according to WHO standard, and toxicity according to National Cancer Institute （NCI） standard. Results There were overall 32 cases evaluated for response to chemotherapy since 4 of 28 patients received two chemotherapy regimens. The complete response （CR） was observed in 5 cases, partial response （PR） in 6 cases, stable disease （SD） in 12 cases, and 9 cases developed progressive disease （PD）. Objective response rate （CR ＋ PR） was 35%, and response plus stable disease （ CR ＋ PR ＋ SD ） was 73%. Seven patients （ 25%, 7/28 ） experienced grade 3 or 4 leucopenia and one （4%, 1/28） grade 4 thrombocytopenia. Non-hematological toxicity mainly was nausea/ vomiting and alopecia. Conclusion The predictive chemotherapy according to MGMT protein expression in patients with malignant gliomas could improve overall response rate with acceptable side-effect, as compared with conventional chemotherapeutic regimen, and thus worth for further investigation.

关 键 词：神经胶质瘤 化学疗法 O^6-甲基鸟嘌呤-DNA甲基转移酶 

分 类 号：R686[医药卫生—骨科学]