Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar;146(3):787-792.
doi: 10.1007/s00432-019-03106-8. Epub 2019 Dec 11.

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

Lazaros Lazaridis  1   2   3   4 , Niklas Schäfer  5 , Sarah Teuber-Hanselmann  6 , Tobias Blau  6 , Teresa Schmidt  1   2   3   4 , Christoph Oster  1   2   3   4 , Johannes Weller  5 , Theophilos Tzaridis  5 , Daniela Pierscianek  7   3   4 , Kathy Keyvani  6 , Christoph Kleinschnitz  8 , Martin Stuschke  9 , Björn Scheffler  2 , Cornelius Deuschl  10 , Ulrich Sure  7   3   4 , Ulrich Herrlinger  5 , Sied Kebir  1   2   3   4 , Martin Glas  11   12   13   14
Affiliations

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

Lazaros Lazaridis et al. J Cancer Res Clin Oncol. 2020 Mar.

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.

Keywords: EF-14; Glioblastoma; Lomustine; NOA-09; TTfields; Temozolomide.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curves with integrated panels indicating the corresponding cumulative event numbers concerning the combination of TTFields/CCNU/TMZ. OS overall survival, PFS progression-free survival
Fig. 2
Fig. 2
Hematoxylin-eosin staining of the primary tumour revealed a diffusely infiltrating astrocytic tumour with high cellularity accompanied by glomeruloid vascular proliferation (arrows) and mitoses leading to the diagnosis of glioblastoma (a). A higher magnification (depicted in b) highlights the pleomorphism of the tumour cells. Nonetheless, multinucleated cells were rare b. Tumour cells of the recurrent tumour tended to be bigger in size and to show some more bi- or multinucleated cells (asterisks); however, true multinucleated giant cells were absent c. Scale bar in a represents 100 µm, scale bars in b and c represent 50 µm
Fig. 3
Fig. 3
Progression pattern of patients with tumour recurrence under TTFields therapy. D diffuse, ND not diffuse
See this image and copyright information in PMC

References

    1. 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. 10.1001/jamaoncol.2016.6020 - PMC - PubMed
    1. 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. 10.1016/S0140-6736(18)31791-4 - PubMed
    1. Kebir S et al (2019) Regorafenib in patients with recurrent high-grade astrocytoma. J Cancer Res Clin Oncol 145:1037–1042. 10.1007/s00432-019-02868-5 - PMC - PubMed
    1. 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. 10.1093/annonc/mdv308 - PubMed
    1. Silginer M, Weller M, Stupp R, Roth P (2017) Biological activity of tumor-treating fields in preclinical glioma models. Cell Death Dis 8:e2753. 10.1038/cddis.2017.171 - PMC - PubMed

LinkOut - more resources