title: Prolonged Temozolomide Maintenance Therapy in Newly Diagnosed Glioblastoma.
abstract: The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS).
  
  
  
  In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded.
  
  
  
  Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77,p= .46).
  
  
  
  Our data do not support a general extension of TMZ maintenance therapy beyond six cycles.The Oncologist2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in prospective randomized clinical trials. We compared the effect of more than six cycles of TMZ in comparison with exactly six cycles on overall survival (OS) and progression-free survival (PFS) by multivariate analysis and found a benefit in PFS but not OS. Thus, our data do not suggest prolonging TMZ maintenance therapy beyond six cycles, which should be considered in neurooncological practice.
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany marco.skardelly@med.uni-tuebingen.de.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Skardelly
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Dangel
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Gohde
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Noell
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Behling
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Lepski
authors.affiliation: Department of Vascular Neurology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Borchers
authors.affiliation: Department of Vascular Neurology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Marilin
authors.initials: M
authors.lastname: Koch
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Vascular Neurology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Institute of Pathology and Neuropathology, Division of Neuropathology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Vascular Neurology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Neuroradiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Bisdas
authors.affiliation: Department of Institute of Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Naumann
authors.affiliation: Department of Radiation Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Paulsen
authors.affiliation: Department of Radiation Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany.|Center for Personalized Medicine, Eberhard Karls University of Tübingen, Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: Medistat GmbH, Kiel, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: von Hehn
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Ritz
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany.
authors.forename: Marcos Soares
authors.initials: MS
authors.lastname: Tatagiba
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Vascular Neurology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Center for CNS Tumors, Comprehensive Cancer Center Tübingen Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany.|Center for Personalized Medicine, Eberhard Karls University of Tübingen, Tübingen, Germany.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Tabatabai
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Glioblastoma; Maintenance chemotherapy; Risk factors; Temozolomide