MGMT表达指导下的复发恶性胶质瘤挽救性化疗疗效分析(附30例报告)

Efficacy of Salvage Chemotherapy based on MGMT Protein Expression in Patients with Recurrent Malignant Gliomas: A Report of 30 Cases

目的:O^6-甲基鸟嘌呤-DNA甲基转移酶(O^6-methylguanine-DNA methyltransferase,MCMT)是与恶性胶质瘤对替莫唑胺(temozolomide,TMZ)等烷化剂耐药相关的重要指标。本文总结根据MCMT表达状态选择不同的化疗方案,对复发恶性胶质瘤患者进行挽救性化疗的临床疗效。方法:经手术后病理确诊的复发恶性胶质瘤患者30例,均有可评价病灶应用免疫组化法检测肿瘤MGMT表达状态,分为阳性组和阴性组。阳性组患者应用非TMZ常规5天方案或非烷化剂药物进行化疗,阴性组患者不限制化疗方案。结果:全组患者客观有效率为20%,中位无进展生存时间为8个月(95%CI:4.3～11.7),中位生存时间为16个月(95%Cl:7.4～24.6) 其中MCMT阳性组16例,阴性组14例阳性组和阴性组患者的客观有效率分别为18.8%和21.4%,中位无进展生存时间分别为7个月(95%Cl:3.1～10.9)和8个月(95%CI:3.9～12.1),中位生存时间分别为16个月(95%CI:5.4～26.6)和16个月(95%CI:7.3～24.7),差异均无统计学意义(P>0.05)结论:复发恶性胶质瘤挽救性化疗具有良好的临床获益,根据肿瘤MGMT表达进行个体化化疗,特别是对于MGMT阳性复发恶性胶质瘤患者,能够避免耐药。

Objective： 0^6-methylguanine-DNA methyltransferase （ MGMT ） is a key marker correlated with the tolerance of malignant glioma to alkylating agents, such as temozolomide （ TMZ ）. The objective of the present study was to evaluate the efficacy of salvage chemotherapy based on the MGMT protein expression in recurrent malignant gliomas. Methods： Thirty patients with pathologically confirmed malignant gliomas were enrolled. The focus of infection was appraisable in all patients. MGMT protein expression was determined by immunohistochemistry. The patients were classified into positive （ PosG ） and negative （ NegG ） groups. A 5-day chemotherapy with non-TMZ conventional regimen or non-alkylating agents was administered to the PosG patients, whereas no restrictive chemotherapeutic regimen was administered to the NegG patients. Results： Based on all patients, the objective response rate （ ORR ） was 20.0%, the median progression-free survival time （ MPFST ） was 8 months （ 95% CI： 4.3-11.7 ）, and the median overall survival time （ MOST ） was 16 months （ 95% CI： 7.4-24.6 ）. Of the 30 tumor cases, 16 were MGMT-positive, whereas 14 were MGMT-nega- tive. The ORRs of the PosG and NegG patients were 18.8% and 21.4% （ P 〉 0.05 ）, respectively. MPFST values were 7 （ 95% CI： 3.1-10.9 ） and 8 months （95 % CI： 3.9-12.1）, respectively, whereas MOST values were 16 （ 95% CI： 5.4-26.6 ） and 16 months （ 95% CI： 7.3-24.7 ）, respectively. No statistically significant differences （ P 〉 0.05 ） were obtained. Conclusion： Salvage chemotherapy is of clinical benefit for patients with recurrent malignant gliomas. Individualized chemotherapy based on the MGMT protein expression, especially for patients with MGMT positive tumor, can improve drug resistance, and attain the same curative effect as that in patients with MGMT-negative tumor.