Chemotherapy for Glioma

Chemotherapeutic treatment of malignant gliomas is extremely challenging. Tumor accumulation of systemically-administrated chemotherapy is always hindered by the blood-brain barrier(BBB). Although temozolomide administered orally or intravenously represents the standard of care for malignant gliomas, its efficacy is unsatisfactory. Local chemotherapy bypasses the BBB and, therefore, achieves a high drug concentration at the site the drug is administered. Carmustine wafers are clinically available local chemotherapeutic agents. However, their efficacy is limited because of limited drug penetration into the tumor. Combined with the highly chemoresistant features of glioma itself, ongoing chemotherapy is far from satisfactory in terms of efficacy. This review covers several important issues regarding temozolomide chemotherapy, including the reactivation of hepatitis B virus, assessment of MGMT promoter methylation, and pseudo-progression. Local chemotherapy for newly diagnosed resectable glioblastoma cases using carmustine wafers is currently under investigation with a randomized phase 3 trial (JCOG 1703), which will also be discussed. In addition, recent progress in convection-enhanced delivery of chemotherapeutics against gliomas has also been reported. Development of an alternative strategy to effectively deliver drugs to the tumor site may improve the efficacy of chemotherapy against gliomas in the near future.