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Bioengineering 2019, 6(1), 11; https://doi.org/10.3390/bioengineering6010011

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

1
Medical Oncology, St Salvatore Hospital, 67100 L’Aquila, Italy
2
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
3
Department of Pathology, St Salvatore Hospital, 67100 L’Aquila, Italy
4
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
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Abstract

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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