title: Metronomic chemotherapy with daily low-dose temozolomide and celecoxib in elderly patients with newly diagnosed glioblastoma multiforme: a retrospective analysis.
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.
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
authors.forename: Grit
authors.initials: G
authors.lastname: Welzel
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Gehweiler
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Brehmer
authors.affiliation: CLC Bio, Aarhus, Denmark.
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Appelt
authors.affiliation: Department of Neuropathology, Ruprecht-Karls-University Heidelberg, and Clinical Cooperation Unit Neuropathology, and DKTK, DKFZ, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Seiz-Rosenhagen
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schmiedek
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany. frank.giordano@umm.de.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Giordano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D000068579:Celecoxib / Q000008:administration & dosage* / Q000009:adverse effects; D059248:Chemoradiotherapy; D015897:Comorbidity; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D012189:Retrospective Studies; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D003606:Dacarbazine; D000068579:Celecoxib; D000077204:Temozolomide
keywords: Chemotherapy; Elderly patients; Glioblastoma