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Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma

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Abstract

Purpose

In the EF-14 trial for newly diagnosed glioblastoma (ndGBM) patients addition of Tumour Treating Fields (TTFields) to temozolomide treatment resulted in a significantly improved overall survival (OS). In the NOA-09/CeTeG trial, combination of lomustine and temozolomide was superior to temozolomide monotherapy in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylated (MGMTm) ndGBM. We evaluated combination of these two treatment modalities in patients with MGMTm ndGBM. There have been so far no data on the combination of these two efficient regimens.

Methods

This bicentric retrospective analysis investigated 16 patients. Parameters evaluated included safety outcome as measured by Common Toxicity Criteria for Adverse Events (CTCAE), clinical outcomes, and compliance to treatment.

Results

Hematologic adverse events CTCAE ≥ 3 were observed in seven, hepatotoxic adverse events of CTCAE ≥ 3 in four patients. Mild to moderate skin toxicity was detected in six patients. At data cutoff, patients demonstrated a median progression-free survival (PFS) of 20 months. The usage rate of TTFields showed a high median adherence (83%) to the therapy.

Conclusions

This analysis provides first indication that the combination of TTFields/lomustine/temozolomide is safe and feasible. The observed survival outcomes might suggest potential beneficial effects.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

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Author information

Conceptualisation: Lazaros Lazaridis, Sied Kebir, and Martin Glas. Methodology: Lazaros Lazaridis, Sied Kebir, and Martin Glas. Formal analysis and investigation: Lazaros Lazaridis, Niklas Schäfer, Sarah Teuber-Hanselmann, Tobias Blau, Sied Kebir, and Martin Glas. Writing-original draft preparation: Lazaros Lazaridis, Sied Kebir, and Martin Glas. Writing-review and editing: Lazaros Lazaridis, Niklas Schäfer, Sarah Teuber-Hanselmann, Tobias Blau, Teresa Schmidt, Christoph Oster, Johannes Weller, Theophilos Tzaridis, Daniela Pierscianek, Kathy Keyvani, Christoph Kleinschnitz, Martin Stuschke, Björn Scheffler, Cornelius Deuschl, Ulrich Sure, Ulrich Herrlinger, Sied Kebir, and Martin Glas. Supervision: Sied Kebir, Martin Glas.

Correspondence to Martin Glas.

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Conflict of interest

L. Lazaridis received speaker honorarium and travel support from Novocure. N. Schäfer reports personal fees and other support from Roche. T. Schmidt received travel support from Novocure. U. Herrlinger reports grants from German Federal Ministry of Education and Research, grants and personal fees from Roche, personal fees and non-financial support from Medac, personal fees and non-financial support from Bristol-Myers Squibb, personal fees from Novocure, personal fees from Novartis, personal fees from Daichii-Sankyo, personal fees from Noxxon, personal fees from Abbvie, personal fees from Bayer, and personal fees from Jansen. S. Kebir received honoraria and travel support from Novocure. M. Glas reports personal fees and other from Novartis, personal fees and other from Daiichi Sankyo, personal fees and other from Novocure, personal fees and other from Medac, personal fees and other from Merck, personal fees and other from Kyowa Kirin, personal fees and other from Bayer, personal fees and other from Jansen-Cilag, personal fees and other from Abbvie. All remaining authors have declared no conflicts of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (ethics committee University Duisburg-Essen; reference number: 18-8428-BO) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

For this type of study (retrospective and anonymous analysis) formal consent is not required.

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Lazaridis, L., Schäfer, N., Teuber-Hanselmann, S. et al. Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma. J Cancer Res Clin Oncol 146, 787–792 (2020). https://doi.org/10.1007/s00432-019-03106-8

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Keywords

  • Glioblastoma
  • TTfields
  • EF-14
  • NOA-09
  • Temozolomide
  • Lomustine