Zhang Jun-Ping, Shi Hong-Liu, Sai Ke, Yue Wei-Ying, Mu Yong-Gao, Zhang Xiang-Heng, Chen Zhong-Ping
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Ai Zheng. 2006 Dec;25(12):1533-7.
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 O6-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.
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.
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.
Individualized chemotherapy based on in vitro CSRAs and MGMT expression for patients with malignant glioma could improve overall response rate.
恶性胶质瘤细胞对大多数化疗药物耐药。亚硝基脲和替莫唑胺（TMZ）是治疗恶性胶质瘤的主要药物。恶性胶质瘤对这些药物的耐药性常与高水平的DNA修复蛋白O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）有关。本研究旨在根据化疗敏感性和耐药性检测（CSRAs）及MGMT表达模式，评估个体化化疗对恶性胶质瘤的疗效，并观察不良事件。
选取2001年12月至2006年2月在中山大学肿瘤防治中心接受手术治疗的经病理确诊的恶性胶质瘤患者。术中获取的新鲜肿瘤组织立即送检，采用MTT法进行CSRAs检测。采用免疫组织化学法检测MGMT蛋白的表达。放疗后，患者根据CSRAs和MGMT表达结果接受化疗。根据WHO标准评估患者对化疗的反应，根据美国国立癌症研究所（NCI）标准评估毒性。
对42例患者进行了化疗反应评估。7例患者连续接受了2种化疗方案，因此，总计49例患者可评估。在这49例患者中，6例（12%）达到完全缓解（CR），10例（20%）达到部分缓解（PR），20例（41%）病情稳定（SD），13例（27%）病情进展（PD）。客观缓解率（CR和PR）为33%，疾病控制率（CR、PR和SD）为73%。血液学毒性是本研究中观察到的主要不良事件，包括IV级贫血（1%）、III-IV级白细胞减少（28%）和III-IV级血小板减少（8%）。非血液学毒性主要包括恶心/呕吐（1%）、疲劳（28%）和脱发（8%）。
基于体外CSRAs和MGMT表达的恶性胶质瘤患者个体化化疗可提高总体缓解率。
