Artikel
Concomitant application of Tumour Treating Fields (TTFields), temozolomide and lomustine in glioblastoma cancer cells in vitro suggests efficacy benefit
Die gleichzeitige Anwendung von Tumor Treating Fields (TTFields), Temozolomid und Lomustin bei Glioblastomzellen in vitro lässt auf Wirksamkeitsvorteile schließen
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Veröffentlicht: | 25. Mai 2022 |
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Objective: Treatment for newly diagnosed glioblastoma (ndGBM) includes temozolomide (TMZ) chemotherapy; however, more than half of patients do not show response. Tumor Treating Fields (TTFields) therapy concomitant with maintenance TMZ represents an important advance in treatment of patients with ndGBM and is recommended in various treatment guidelines. Recently, lomustine (CCNU) together with TMZ demonstrated improved overall and progression-free survival following resection and radiochemotherapy in patients with ndGBM and methylated O(6)-methylguanine-DNA methyltransferase (MGMT) promoter. This study investigated the efficacy of concomitant application of TTFields with TMZ and CCNU in GBM cells in vitro.
Methods: Using the inovitro system, GBM cells (U-87 MG and LN229) were treated for 72 h with TTFields at a frequency of 200 kHz and an intensity of 1 V/cm RMS. To examine the efficacy of combining TTFields with TMZ and/or CCNU we measured cell survival, clonogenic potential, overall effect (product of cytotoxicity multiplied with clonogenicity), and apoptosis induction.
Results: Combination of TMZ and TTFields resulted in enhanced cytotoxicity in comparison to each single treatment. The cytotoxic effect we observed when co-applying CCNU with TTFields suggested a synergistic interaction between the two treatment modalities. The clonogenic, overall, and apoptotic effects of TMZ and CCNU were increased as well following co-treatment with TTFields. The triple combination of TTFields with both TMZ and CCNU showed better efficacy than TMZ/CCNU or TTFields alone.
Conclusion: The here presented study suggests potential better efficacy in treating GBM by concomitantly applying TTFields with TMZ/CCNU.