Temozolomide in malignant gliomas

Glioblastoma multiforme and anaplastic astrocytoma are the most common primary central nervous system malignancies and are the major cause of morbidity/ mortality despite combined modality approaches. Temozolomide (TMZ), a novel, oral, second-generation alkylating agent, has demonstrated antitumor activity against a broad range of solid tumors and highly resistant malignancies, including high-grade glioma Temozolomide does not require hepatic metabolism for activation, rapidly penetrates the cerebrospinal fluid, and consistently demonstrates reproducible linear pharmacokinetics with approximately 100% oral bioavailability. In preliminary clinical studies, TMZ has demonstrated meaningful efficacy and an acceptable safety profile in the treatment of patients with malignant glioma. These results have been recently confirmed in three open-label, multi-institutional studies that evaluated the use of TMZ in 525 malignant glioma patients. These studies represent the largest evaluation of a single agent in patients with recurrent malignant gliomas and were rigorously controlled with strict, prospectively defined criteria for assessment of tumor response, central review of histology, and validated instruments to assess health-related quality of life. Temozolomide was effective in delaying disease progression and maintaining health-related quality of life. Temozolomide represents a promising new agent in the treatment of malignant glioma.