[Treatment of glioma with temozolomide]

Abstract

Older patients are frequently excluded from randomized studies; further, it is unclear whether the morbidity associated with chemoradiotherapy with temozolomide (TMZ) outweighs the possible survival benefit in this population. TMZ administered at a dose of 150-200 mg/m2 for 5 days every 4 weeks is the standard of care in operated glioblastoma (GBM) after concurrent chemoradiotherapy. Alternative dosing regimens, such as 1-week on/1-week off, or 3-week on/1-week off, that deliver more prolonged exposure have been observed to result in higher cumulative doses than the standard 5-day regimen and may deplete tumor-derived O6-methylguanine-DNA methyltransferase (MGMT) in tumor cells, thus sensitizing tumor cells to the effects of TMZ. Currently, chemotherapy with TMZ is an interesting alternative to radiotherapy in patients with very large tumors or in the elderly who are exposed to a higher risk of delayed neurotoxicity. The DNA damage induced by nitrosoureas and TMZ is partially repaired by MGMT. Thus, administration of the combination of nitrosoureas and TMZ might overcome MGMT-mediated resistance via MGMT depletion, yielding superior treatment results compared to the administration of treatment alone. However, the results of 2 studies that administered BCNU and CCNU with TMZ reported contradictory results. The introduction of TMZ has enabled the extension of chemotherapy treatment by 1-3 years due to the improved toxicity profile and lack of cumulative toxicity. Treatment-induced myelodysplastic syndrome with or without acute myeloblastic leukemia is a well-recognized late treatment-related complication associated with TMZ administration.