What is the role of temozolomide in the treatment of glioblastoma multiforme (GBM)?

Updated: Jul 01, 2019
  • Author: Jeffrey N Bruce, MD; Chief Editor: Herbert H Engelhard, III, MD, PhD, FACS, FAANS  more...
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Evidence suggests that in patients over 60 years old, treatment with temozolomide is associated with longer survival than treatment with standard radiotherapy, and for those over 70 years old, temozolomide or hypofractionated radiotherapy is associated with prolonged survival than treatment with standard fractionated radiotherapy. The improvement in survival with temozolomide is enhanced in patients with MGMT promoter methylation.Data from a a randomised phase 3 trial suggests that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter. [55] Stupp et al reported the final results of the randomized phase III trial for patients with glioblastoma who were treated with adjuvant temozolomide and radiation with a median follow-up of more than 5 years. [55]  

Stupp et al reported the final results of the randomized phase III trial for patients with glioblastoma who were treated with adjuvant temozolomide and radiation with a median follow-up of more than 5 years. Stupp et al previously reported improved median and 2-year survival when temozolomide was added to radiation therapy in glioblastoma. Survival in the combined therapy group (ie, temozolomide and radiation) continued to exceed that of radiation alone throughout the 5-year follow-up (p< 0.0001). Survival of patients who received adjuvant temozolomide with radiotherapy for glioblastoma is superior to radiotherapy alone across all clinical prognostic subgroups. [56]   

Median time to recurrence after standard therapy is 6.9 months. [57] For recurrent glioblastoma multiforme, surgery is appropriate in selected patients, and various radiotherapeutic, chemotherapeutic, biologic, or experimental therapies are also employed. [58, 35]

Approximately 90% of glioblastomas express cytomegalovirus (CMV) proteins, and Batich et al have reported benefit with a dendritic cell vaccine targeting CMV antigen pp65, using CMV as a proxy for glioblastoma. Patients are first treated with dose-intensified temozolomide, as the temozolomide induces lymphopenia, which provides an opportunity to retrain the immune system.

In a study of 11 patients with newly diagnosed glioblastoma received temozolomide, 100 mg/m2/d × 21 days per cycle, and at least three pp65-directed vaccines admixed with granulocyte-macrophage colony-stimulating factor on day 23 ± 1 of each cycle. Despite increased proportions of regulatory T cells (Tregs), median progression-free survival was 25.3 months and overall survival was 41.1 months; three patients remained progression-free more than 7 years after diagnosis. [59]

Wernicke et al report that prostate-specific membrane antigen is expressed in the vasculature of GBM vessels and represents a potential novel therapeutic vascular target. Future clinical trials are planned. [60]


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