Clinical outcome of an alternative fotemustine schedule in elderly patients with recurrent glioblastoma: a mono-institutional retrospective study

J Neurooncol. 2016 Jul;128(3):481-6. doi: 10.1007/s11060-016-2136-7. Epub 2016 May 11.


The optimal treatment of recurrent glioblastoma (GBM) in elderly patients is unclear. Fotemustine (FTM) is a third-generation nitrosourea showing efficacy in gliomas and it has been used with different schedules in adult patients. We performed, for the first time anywhere, a mono-institutional retrospective study to analyze the clinical outcome of an alternative fotemustine schedule in elderly patients with recurrent GBM. Retrospectively, we analyzed all GBM patients 65 years or older previously treated with the combination of radiation therapy and temozolomide (TMZ), receiving an alternative FTM schedule as second-line treatment at our Oncological Center from October 2011 to October 2014 with an ECOG PS ≤ 2. FTM was administrated at 80 mg/m(2) every 2 weeks for five consecutive administrations (induction phase), and then every 4 weeks at 80 mg/m(2) as maintenance. We enrolled 44 patients, 33 males and 11 females; average age was 70 years. ECOG PS was 0-1 in 80 % of the patients. 38 patients relapsed during temozolomide (TMZ) therapy. MGMT methylation status was analyzed in 34 patients and MGMT was methylated in 53 % of the patients. The median progression free survival (PFS) and overall survival (OS) from FTM treatment was 4.1 months (95 % CI 3.1-5.2) and 7 months (95 % CI 5.2-8.4), respectively. Patients with MGMT methylated status and patients who relapsed after completing TMZ therapy had a longer PFS and OS from the beginning of FTM. Thrombocytopenia was the most frequent grade 3-4 haematological toxicity (9 %). The alternative schedule of FTM may be an active and safe treatment for elderly patients with recurrent glioblastoma, especially patients with methylated MGMT and who relapsed after completing temozolomide therapy.

Keywords: Elderly; Fotemustine; Glioblastoma; Temozolomide.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / radiotherapy
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Nitrosourea Compounds / administration & dosage*
  • Nitrosourea Compounds / adverse effects
  • Organophosphorus Compounds / administration & dosage*
  • Organophosphorus Compounds / adverse effects
  • Recurrence
  • Retrospective Studies
  • Survival Analysis
  • Temozolomide
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics


  • Antineoplastic Agents
  • Nitrosourea Compounds
  • Organophosphorus Compounds
  • Tumor Suppressor Proteins
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • fotemustine
  • Temozolomide