Optimal role of temozolomide in the treatment of malignant gliomas

Temozolomide (TMZ) is an alkylating agent that was approved for anaplastic astrocytoma and glioblastoma. Its role in the treatment of recurrent disease has been confirmed, and more importantly, alternative treatment schedules and combination regimens have been developed. A recent phase III trial has demonstrated a survival advantage for concomitant TMZ administration with radiotherapy in patients with newly diagnosed glioblastoma. Molecular studies suggest a strong predictive role of the DNA repair enzyme O6-methyl-guanine-DNA-methyl-transferase (MGMT) and outcome of TMZ-based chemotherapy. This review summarizes the current knowledge, highlights approved and nonapproved indications, and describes molecular studies that may allow us to identify the patients most likely to benefit from this treatment.