选择性化疗方案治疗恶性胶质瘤的疗效和生存情况分析

Personalized Chemotherapy Based on O6-methylguanine-DNA methyltransferase (MGMT) Expression Pattern for Glioma Patients

背景与目的：O^6-甲基鸟嘌呤-DNA甲基转移酶（O^6-methylguanine-DNA methyhransferase，MGMT）表达与胶质瘤患者的化疗耐药相关。本研究总结MGMT高表达和低表达恶性胶质瘤患者的化疗方案、近期疗效和生存情况．分析选择性化疗是否对MGMT高表达患者有益。方法：自2000年8月至2006年1月，中山大学肿瘤防治中心神经肿瘤科收治的经手术后病理确诊的成人恶性脑胶质瘤患者57例．所有病例化疗前均有可评价病灶。化疗前用免疫组化方法检测肿瘤组织MGMT表达情况．对MGMT高表达者．尽量避免使用亚硝脲类或替莫唑胺单药化疗，采用不含亚硝脲类或替莫唑胺方案，或由替莫唑胺（temozolomide，TMZ）和顺铂组成联合化疗方案；或亚硝脲类药物、替莫唑胺分别与其他细胞毒药物组成联合化疗方案（VM-26、DDP、CBP、IFO、VP16）；对MGMT低表达者，不限制亚硝脲类药物或替莫唑胺的应用。结果：35例患者MGMT高表达，22例MGMT低表达，MGMT低表达组的客观有效率（objective response，OR）和疾病控制率（response rate，RR）高于MGMT高表达组（40．9％：22．9％和72．7％：60.0%．但差异无统计学意义（P〉0．05）。57例中位随访时间11．7个月（0．7～53．4）。MGMT低表达组和高表达组中位无疾病进展时间（Drogressive-free survival，PFS）分别是8．5个月（95％CI 4．8—19．3）和6．7（95％CI 3．7—9．3），中位生存时间（overail survival，OS）分别是20．3（95％CI 14．3～）和16．105％CI 11．1～26．2），中位PFS和0S在MGMT低表达组和高表达组差异无统计学意义（P〉0．05）。结论：在化疗前检测恶性胶质瘤MGMT表达情况，对MGMT高表达患者选用有助于克服耐药的化疗方案进行选择性化疗。可使MGMT高表达患者的近期疗效（客观有效率和疾病控制率）和生存时间（无疾病进展生存和总生存）达到MGMT低表达患者水平。

BACKGROUND ＆ OBJECTIVE：Expression of O^6-methylguanine-DNA methyltransferase （MGMT） has been related to drug resistance of glioma patients. This article is to analyze whether personalized chemotherapy based on MGMT expression could be benefit to patients with MGMT positive gliomas. METHODS：There were 57 malignant glioma patients （anaplastie oligodendroglioma, AO 3 eases, anaplastic astrocytoma, AA 36 cases, glioblastoma multiforme, GBM 18 eases） received chemotherapy in Cancer Center of Sun Yat-sen University, based on MGMT expression, and response as well as survival time were evaluated. Thirty-five patients with MGMT positive tumors received chemotherapy regimens, which consisted of no-alklating agent regimen or cisplatin plus TMZ regimen, or combination of TMZ or nitrosoureas with no-alklating agent （teniposide （VM-26）, cisplatin （DDP）, carboplatin （CBP）, isophosphamide （IFO）, etoposide （VP16））. While 22 patients with MGMT negative tumors, there was no restriction on chemotherapy regimen. That was eigther nitrourea or TMZ had been used in the regimen, and the most commonly used regimen were PCV;TMZ ＋VM26; MeCCNU ＋VM26. RESULT： Although objective response （OR） and response rate （RR） in the patients with MGMT negative tumors were higher than that in the patients with MGMT positive tumors, but there was no statistical significance between those two groups （P 〉0.05）. By following up 0.7-53.4 months （mean 11.7 months）, progressive-free survival （PFS） in MGMT negative and positive patients were 8.5 months（95% CI 4.8-19.3） and 6.7 months（95% CI 3.7-9.3）, and overall survival（OS） were 20.3 months （95% CI 14.3-） and 16.1 months （95% CI 11.1-26.2, respectively. （P〉0.05）. CONCLUSIONS：Our results indicated that personized chemotherapy for glioma patients based on MGMT expression can obtain satisfactory results especially for patients with MGMT positive gliomas.