Management of central nervous system (CNS) malignancies continues to be a therapeutic challenge. Both primary and secondary (metastatic) CNS tumors are frequently resistant to commonly used chemotherapeutic agents. Surgery and radiotherapy provide palliation of symptoms but usually do not lead to curative outcomes. Alkylating agents have been used in the therapy of primary brain cancer for several decades. This group of medications has the ability to penetrate blood-brain barrier, achieving cytotoxic concentrations in cerebrospinal fluid and brain parenchyma. Temozolomide is a second-generation alkylating chemotherapeutic agent, introduced to therapy of primary brain tumors in the 1990s. It has since been approved for the therapy of recurrent and newly diagnosed malignant glioma. Temozolomide offers improved outcomes when used alone or in combination with irradiation. Its role in the therapy of other types of brain cancer, and specifically primary CNS lymphoma, continues to develop. This review will discuss the early stages of development of temozolomide, its introduction into the therapy of glioma, its role in the therapy of elderly patients, mechanisms of resistance and the evolution of its current and future applications.
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