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Selection of chemotherapy for glioblastoma expressing O6-methylguanine-DNA methyltransferase

Authors:
Yasuo Iwadate, Tomoo Matsutani, Yuzo Hasegawa, Natsuki Shinozaki, Takashi Oide, Toru Tanizawa, Yukio Nakatani, Naokatsu Saeki, Shuichi Fujimoto

Affiliations:
Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan. iwadatey@faculty.chiba-u.jp

Doi:
10.3892/etm_00000009

Pages:
53-57

Abstract:

The therapeutic benefit of nitrosoureas or temozolomide for glioblastoma is limited mainly by O6-methylguanine-DNA methyltransferase (MGMT) expression. The aim of this study was to evaluate the effectiveness of various anticancer drugs for MGMT-positive glioblastoma. Seventy-four glioblastoma patients were administered various anticancer drugs according to drug sensitivity testing. For the individualization, drug-induced apoptosis was quantified by flow cytometry in the primary culture of surgically resected tumor cells. The MGMT protein expression was analyzed by immunohistochemistry. The median survival of the patients receiving the individualized chemotherapy was 19.4 months (95% CI, 15.9-22.1). The patients with negative MGMT immunostaining had significantly longer survival than those with positive MGMT immunostaining [median survival, 22.3 months (95% CI, 17.6-27.0) vs. 15.1 months (95% CI, 13.4-16.8); p=0.0188]. For MGMT-positive tumors, the platinum agents and the taxanes were more frequently selected for administration than the other categories of anticancer agents. The patient survival period of MGMT-positive glioblastomas treated with the platinum agents or the taxanes [median survival, 20.1 months (95% CI, 18.0-22.7)] was significantly longer than that of MGMT-positive tumors treated with nitrosoureas (p=0.0026), and was equivalent to that of MGMT-negative glioblastomas (p=0.3047). These results suggest that the platinum agents and the taxanes offer the best probability to be effective against immunohistochemically MGMT-positive glioblastomas.

OPEN ACCESS ARTICLE

Experimental and Therapeutic Medicine

January-February 2010
Volume 1 Number 1


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