難治性悪性神経膠腫の治療戦略

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Malignant gliomas are the most common primary central nervous system tumors. Standard therapy is surgical resection, where possible, and radiotherapy. Since adjuvant chemotherapy only provides a modest survival benefit, new therapies are necessary. Recently developed agents, such as temozolomide (TMZ), irinotecan, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), have demonstrated efficacy against malignant gliomas. A novel oral alkylating agent, TMZ shows good penetration in the central nervous system, and it has largely replaced nitrosoureas in the treatment of gliomas. Recently, a randomized trial in which newly diagnosed glioma patients were treated with TMZ and radiation achieved enhanced survival rates. In particular, better survival rates were observed in patients with a methylated promotor of the O^6-methylguanine-DNA methyltransferase (MGMT) gene which encodes an alkyltransferase. Another clinical study revealed that polymorphisms found in genes encoding topoisomerase I inhibitor irinotecan-metabolizing enzymes (UGT1A1) were associated with the occurrence of severe irinotecan-induced toxicity. Overexpression of EGFR appears to be correlated with the grade of glioma and it has been reported that specific mutations in the EGFR gene are correlated with clinical responsiveness to the EGFR-TKI gefitinib. In order to achieve innovative treatment strategies in the future, it is therefore important for clinical pharmacists to have a good understanding of glioma at the molecular level since this will help in identifying patients most likely to benefit from a specific therapy. We hope that personalized medication for glioma based on genetics will increase drug efficacy and prevent or reduce adverse reactions, which in turn will improve clinical outcomes and decrease the overall costs of therapy.
2006-11-10

難治性悪性神経膠腫の治療戦略

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