Temozolomide, an Oral Alkylating Agent, Effective in Treating Glioblastoma

Decades of clinical chemotherapy trials for newly diagnosed glioblastoma have yielded negative or marginally significant results. Recently, temozolomide, a well-tolerated oral methylating agent that readily crosses the blood-brain barrier, showed single-agent activity against glioblastoma. In vitro data suggested synergy between temozolomide and radiotherapy; and continuous daily temozolomide depleted cells of methylguanine methyltransferase (MGMT), an enzyme important in repairing tumoral DNA damage from alkylating chemotherapeutic agents. A phase II trial of daily low-dose temozolomide with standard radiation, followed by standard-dose temozolomide, in patients with newly diagnosed glioblastoma yielded promising results (J Clin Oncol 2002…