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
Bell EH et al (2017) Molecular-based recursive partitioning analysis model for glioblastoma in the temozolomide era: a correlative analysis based on NRG oncology RTOG 0525. JAMA Oncol 3:784–792. https://doi.org/10.1001/jamaoncol.2016.6020
Herrlinger U et al (2019) Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet 393:678–688. https://doi.org/10.1016/S0140-6736(18)31791-4
Kebir S et al (2019) Regorafenib in patients with recurrent high-grade astrocytoma. J Cancer Res Clin Oncol 145:1037–1042. https://doi.org/10.1007/s00432-019-02868-5
Middleton MR et al (2015) Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma. Ann Oncol 26:2173–2179. https://doi.org/10.1093/annonc/mdv308
Silginer M, Weller M, Stupp R, Roth P (2017) Biological activity of tumor-treating fields in preclinical glioma models. Cell Death Dis 8:e2753. https://doi.org/10.1038/cddis.2017.171
Stupp R et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330
Stupp R et al (2017) Effect of Tumor-Treating Fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 318:2306–2316. https://doi.org/10.1001/jama.2017.18718
Toms SA, Kim CY, Nicholas G, Ram Z (2019) Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial. J Neurooncol 141:467–473. https://doi.org/10.1007/s11060-018-03057-z
Turner SG, Gergel T, Wu H, Lacroix M, Toms SA (2014) The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF-100A system. World J Surg Oncol 12:162. https://doi.org/10.1186/1477-7819-12-162
Wen PY, Chang SM, Van den Bent MJ, Vogelbaum MA, Macdonald DR, Lee EQ (2017) Response assessment in neuro-oncology clinical trials. J Clin Oncol 35:2439–2449. https://doi.org/10.1200/JCO.2017.72.7511
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Contributions
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.
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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.
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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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DOI: https://doi.org/10.1007/s00432-019-03106-8