[Individualized chemotherapy based on drug sensitivity and resistance assay and MGMT protein expression for patients with malignant glioma--analysis of 42 cases].
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Individualized chemotherapy based on in vitro CSRAs and MGMT expression for patients with malignant glioma could improve overall response rate.
Zhang
Jun-Ping
JP
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Shi
Hong-Liu
HL
Sai
Ke
K
Yue
Wei-Ying
WY
Mu
Yong-Gao
YG
Zhang
Xiang-Heng
XH
Chen
Zhong-Ping
ZP
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D002648:Child; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism*; D012074:Remission Induction; D000077204:Temozolomide; D055815:Young Adult
D005047:Etoposide; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002945:Cisplatin; D000077204:Temozolomide