Local delivery of temozolomide via a biologically inert carrier (Temodex) prolongs survival in glioma patients, irrespectively of the methylation status of MGMT

Neoplasma. 2019 Mar 5;66(2):288-293. doi: 10.4149/neo_2018_180613N393. Epub 2018 Dec 12.


Glioma is the most common brain malignancy. Standard first-line therapy for glioma includes surgery, radiotherapy and systemic administration of temozolomide. However, temozolomide does not reach the brain in sufficient doses when administered orally and has poor efficiency in more than half of the patients. Strategies to improve the treatment of glial malignancies are therefore needed. We have recently developed a system (Temodex) for local administration of temozolomide by encapsulating the drug in a biologically inert matrix. Here, we assessed the effect of Temodex in combination with standard therapy in a small-scale clinical study. Since the efficacy of temozolomide therapy is known to depend on the methylation status of the O6-methylguanine-DNA methyltransferase gene (MGMT) promoter, we also analyzed whether the effect of Temodex was influenced by the methylation status of MGMT. Our data show that the combination of standard therapy and Temodex was more efficient than standard therapy alone, promoting the overall patient survival by up to 33 weeks. Moreover, the efficacy of Temodex was not dependent on the methylation status of MGMT. Local Temodex administration in combination with standard therapy thereby emerges as a novel therapeutic option, with applicability that is independent on the methylation status of the MGMT promoter.

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Brain Neoplasms / drug therapy*
  • DNA Methylation
  • DNA Modification Methylases / chemistry
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / chemistry
  • DNA Repair Enzymes / genetics
  • Drug Carriers / chemistry*
  • Glioma / drug therapy*
  • Humans
  • Promoter Regions, Genetic
  • Temozolomide / administration & dosage*
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics


  • Antineoplastic Agents, Alkylating
  • Drug Carriers
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide