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Bioengineering 2019, 6(1), 11;

Looking for A Place for Dose-Dense TMZ Regimens in GBM Patients: An Experience with MGMT Exploratory Evaluation

Medical Oncology, St Salvatore Hospital, 67100 L’Aquila, Italy
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Department of Pathology, St Salvatore Hospital, 67100 L’Aquila, Italy
Department of Neurosurgery, St Salvatore Hospital, 67100 L’Aquila, Italy
Author to whom correspondence should be addressed.
Received: 18 December 2018 / Revised: 19 January 2019 / Accepted: 21 January 2019 / Published: 22 January 2019
PDF [437 KB, uploaded 30 January 2019]


Prolonged exposure to temozolomide (TMZ) could improve clinical outcomes in recurrent glioblastoma multiforme (GBM) patients. We previously developed a dose-dense regimen of TMZ in a phase II study (180 mg/m2 from days 1 to 5 every two weeks). A retrospective analysis of patients with macroscopic residual GBM treated with “post-induction” dose-dense TMZ was conducted, adding an explorative subgroup analyses among patients with different O6-methylguanine DNA methyltransferase (MGMT) expressions (negative vs positive, < vs ≥ of 50 % of cells stained, < vs ≥ 70% of cells stained). Thirty-six patients were evaluated; after a median follow-up of 36 weeks, median Progression Free Survival (PFS) and median Overall Survival (OS) were 19 and 34 weeks, respectively. MGMT expression (70% cut-off) and sex were confirmed as independent predictors for disease control rate (DCR) at multivariate analysis. At univariate analysis ECOG-PS, Sex (female), extensive tumor resection was shown to be related to a longer PFS, while MGMT expression (cut-off 70%) to a shorter PFS. Multivariate analysis with Cox hazard regression confirmed only ECOG-PS as an independent predictor for PFS. ECOG-PS showed to be significant related to a longer OS. Our analysis showed that dose-dense TMZ regimens are still an option for patients with recurrent GBM, but should be used for re-challenge treatments. MGMT immunohistochemistry high expression might be used as a “surrogate” negative predictor for DCR for dd-TMZ treatments. View Full-Text
Keywords: glioblastoma multiforme; dose-dense; temozolomide; MGMT glioblastoma multiforme; dose-dense; temozolomide; MGMT

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Napoleoni, L.; Cortellini, A.; Cannita, K.; Parisi, A.; Dal Mas, A.; Calvisi, G.; Venditti, O.; Lanfiuti Baldi, P.; Cocciolone, V.; Ricci, A.; Ficorella, C. Looking for A Place for Dose-Dense TMZ Regimens in GBM Patients: An Experience with MGMT Exploratory Evaluation. Bioengineering 2019, 6, 11.

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