Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma
- 11 April 2017
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 88 (15), 1422-1430
- https://doi.org/10.1212/wnl.0000000000003809
Abstract
Objective: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. Methods: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome. Results: Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7–20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7–23.3, vs 17.2 months, 95% CI 10.2–24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9–36.4, vs 33.2 months, 95% CI 25.3–41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4–1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8–3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status. Conclusion: These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles. Classification of evidence: This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS.This publication has 32 references indexed in Scilit:
- Distinct molecular mechanisms of acquired resistance to temozolomide in glioblastoma cellsJournal of Neurochemistry, 2012
- Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomasInternational Journal of Cancer, 2011
- Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified TemozolomideInternational Journal of Radiation Oncology*Biology*Physics, 2010
- Molecular Predictors of Progression-Free and Overall Survival in Patients With Newly Diagnosed Glioblastoma: A Prospective Translational Study of the German Glioma NetworkJournal of Clinical Oncology, 2009
- Prognostic Significance of Molecular Markers and Extent of Resection in Primary Glioblastoma PatientsClinical Cancer Research, 2009
- Randomized Phase II Trial of Chemoradiotherapy Followed by Either Dose-Dense or Metronomic Temozolomide for Newly Diagnosed GlioblastomaJournal of Clinical Oncology, 2009
- Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trialThe Lancet Oncology, 2009
- Safety and feasibility of long-term temozolomide treatment in patients with high-grade gliomaNeurology, 2007
- Radiotherapy plus Concomitant and Adjuvant Temozolomide for GlioblastomaThe New England Journal of Medicine, 2005
- Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant TemozolomideJournal of Clinical Oncology, 2002