Management of patients with newly diagnosed malignant primary brain tumors with a focus on the evolving role of temozolomide

The prognosis for patients with newly diagnosed malignant gliomas remains poor; however there have been some recent advances in treatment that have generated optimism. Medical management usually includes administration of corticosteroids to control peritumoral edema. Anticonvulsants are indicated for patients with established tumor-related seizures; however, the prophylactic use of anticonvulsants remains controversial. Advances in neurosurgical techniques have improved the safety of tumor resection and most patients undergo the maximal safe surgical debulking of tumor. The tissue sample obtained provides conclusive pathologic diagnosis and tumor classification and extensive tumor resection may impact patient outcome. For glioblastoma, external beam radiation had been the conventional first line treatment; however a recent international phase III trial has provided level 1 evidence that a chemoradiation regimen using external beam radiation plus the oral chemotherapy agent temozolomide provides a survival advantage over radiation alone. Correlative studies were also performed that demonstrated better outcomes for patients with tumors demonstrating methylation (inactivation) of the promoter region of methyl guanine methyltransferase (MGMT) gene. Additional studies are in progress building on the clinical trial results using different dosing schedules of temozolomide and combination regimens. Studies are also underway to develop molecular markers, such as expression of MGMT that may help select the patients most likely to benefit from this treatment.