MGMT表达指导恶性胶质瘤的替莫唑胺化疗(附40例报告)

摘要

目的 根据肿瘤组织O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)表达的差异选择不同的替莫唑胺(TMZ)方案对恶性胶质瘤进行化疗,评价其客观疗效、生存率和不良反应.方法 经手术后病理确诊的初治或复发恶性胶质瘤患者40例,均接受过放疗并有残留或复发可评价病灶.采用免疫组织化学方法检测肿瘤组织MGMT表达,将患者分为阳性组和阴性组.阴性组选择TMZ常规5天方案化疗,阳性组选择TMZ小剂量持续或TMZ联合顺铂方案化疗.结果 阴性组22例,阳性组18例.阳性组患者的一般状况比阴性组差,多数为复发患者且既往接受过化疗(P＜0.05).阴性组和阳性组患者的客观有效率分别为31.8%和33.3%,中位无进展生存时间分别为7个月(95%CI:5.7-8.3)和7个月(95%CI:2.3-11.7),中位生存时间分别为24个月(95%CI:12.7-35.3)和11.5个月(95%CI:9.9-11.3),差异均无统计学意义(P＞0.05).主要不良反应为Ⅰ～Ⅱ度的中性粒细胞下降(20%)、食欲下降(30%)、恶心呕吐(22%)和转氨酶升高(25%),联合顺铂方案的中性粒细胞下降发生率高于TMZ单药方案(P＜0.05).结论 TMZ小剂量持续或联合顺铂方案化疗可能改善MGMT阳性恶性胶质瘤患者的临床疗效,耐受性好.%Objective This study was to evaluate the efficacy and toxicity of temozolomide(TMZ)chemotherapy based on O6-methylguanine-DNA methyltransferase (MGMT) protein expression in patients with malignant gliomas.Methods A total of 40 patients with pathologically confirmed malignant gliomas were enrolled.All patients had pretreated with radiotherapy and had assessable lesions.MGMT protein expression were detected by immunohistochemical technique.Alternative schedules of TMZ were administered based on MGMT protein expression.Patients with MGMT negtive expression received 150～200 mg/m2 TMZ on days 1-5.Patients with MGMT postive expression received 75 mg/m2 TMZ on days 1-21 or 150～200 mg/m2 TMZ on days 2-6 combined with Cisplatin (DDP) 40 mg/m2 on days 1-2.Results Among 22 patients with MGMT negative expression and 18 patients with MGMT positive expression,the response rate was 31.8％ and 33.3％ (P ＞0.05 ),the median progression-free survival time was 7 months (95％ CI:5.7-8.3) and 7 months(95％ CI:2.3-11.7 ),the median survival time was 24 months(95％ CI:12.7-35.3) and 11.5 months (95％ CI:9.9-11.3 ),respectively.There were no significant differences (P>0.05 ).The most common toxicities were grade Ⅰ～Ⅱ neutropenia (20％ ),decreased appetite (30％ ),nausea and vomitting (22％ )and elevated liver enzymes (25％ ).Conclusion Alternative schedules of TMZ may improve efficacy in patients with MGMT positive expression tumors,toxicities were tolerable.