Metronomic chemotherapy with daily low-dose temozolomide and celecoxib in elderly patients with newly diagnosed glioblastoma multiforme: a retrospective analysis

J Neurooncol. 2015 Sep;124(2):265-73. doi: 10.1007/s11060-015-1834-x. Epub 2015 Jun 5.

Abstract

Chemotherapy is often omitted in elderly patients with glioblastoma multiforme due to a fear of side effects. We applied metronomic chemotherapy with low-dose temozolomide and celecoxib (LD-TEM/CEL) during and after external beam radiotherapy (EBRT) and here report on how this regimen compares to standard temozolomide radiochemotherapy (SD-TEM) in elderly patients. We retrospectively analyzed records of 146 patients aged 65 years and older that underwent EBRT. Factors of interest were age, performance status, comorbidities, MGMT status, therapy (resection/biopsy, radiotherapy/dose, chemotherapy/regimen/dose), progression-free (PFS) and overall survival (OS) status. Irrespective of the regimen, addition of chemotherapy more than doubled median survival rates (EBRT only: 4.2 months; EBRT + LD-TEM/CEL: 8.5 months; EBRT + SD-TEM: 10.8 months; p ≤ 0.008). Although patients receiving metronomic LD-TEM/CEL were significantly older (62 % were ≥75 years vs. 22 %; p < 0.001), had significantly lower performance scores (50 % had a KPS <70 vs. 28 %; p = 0.049) and were significantly more comorbid (73 % had ≥4 comorbidities vs. 37 %; p = 0.002) than patients of the SD-TEM group, there were no significant differences in PFS and OS. Independent of other factors, omission of chemotherapy significantly impairs progression-free and overall survival. With all the limitations of a retrospective analysis, our data suggest that metronomic chemotherapy with LD-TEM/CEL may be equieffective and eventually better tolerated than SD-TEM. It may be offered to elderly patients that are not eligible for standard chemotherapy.

Keywords: Chemotherapy; Elderly patients; Glioblastoma.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Brain Neoplasms / epidemiology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Celecoxib / administration & dosage*
  • Celecoxib / adverse effects
  • Chemoradiotherapy
  • Comorbidity
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives*
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Glioblastoma / epidemiology
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Grading
  • Retrospective Studies
  • Survival Analysis
  • Temozolomide
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Dacarbazine
  • Celecoxib
  • Temozolomide