Chemotherapy of High-Grade Astrocytomas in Adults

Malignant gliomas have been historically considered unresponsive to chemotherapy due to their intrinsic resistance to conventional anticancer medications and the role of the blood-brain barrier in preventing access of the cytotoxic agents to the tumor. However, recent studies have demonstrated the efficacy of specific drugs in subsets of patients with high-grade astrocytomas that has revived the enthusiasm for the role of systemic chemotherapy against these neoplasms. Temozolomide, a monofunctional alkylator, was the first chemotherapeutic agent to definitively improve survival in adults with newly diagnosed glioblastoma used in combination with radiation therapy with the most pronounced effect being in a subgroup of tumors with MGMT promoter methylation. Various other cytotoxic drugs and their combinations have been tested in this population with mostly anecdotal reports of benefit. Current efforts are directed towards identifying the subsets of patients most likely to benefit from chemotherapy and to determine the most effective treatment regimens likely to improve outcome. In addition, specific strategies in order to overcome resistance mechanisms to cytotoxic drugs and to disable cellular adaptive pathways are being explored to enhance cell kill and antitumor effects of chemotherapeutic agents.