Abstract
Abstract Background: Gastric cancer is the fourth most common cancer and the second most common cause of cancer death worldwide. Despite systemic therapies improvement in recent era, long-term survival rates for patients with advanced gastric cancer remains poor. FOLFOX (Oxaliplatin, 5-FU and Leucovorin) is an approved chemotherapy regimen for treatment of gastric cancer. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. The aim of this work is to explore the potential of the use of TTFields alone and in combination with FOLFOX as a treatment for gastric carcinomas. Methods: AGS and KATO III cells were treated for 72 hours with TTFields (1.1 and 1.7 V/cm, respectively) at various frequencies, using the inovitro system. Efficacy of the combined treatment of TTFields and FOLFOX was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, clonogenic potential and overall effect were determined at the end of treatment. Results: The optimal TTFields frequency leading to the highest reduction in cell counts was found to be 150 kHz for both cell lines resulting in 55% and 52% reduction in cell counts for AGS and KATO III, respectively. In addition, clonogenic potential of both cell lines was reduced by more than 70%. The combined treatment of TTFields with each chemotherapy (Oxaliplatin, 5-FU or Leucovorin), led to a significant reduction in the survival of AGS and KATO III cells (2-way ANOVA, p<0.001 for both cell lines) as compared to each treatment alone. The combined treatment of TTFields with FOLFOX led to further reduction in the overall effect (cytotoxic and clonogenic) of AGS (79%) compared to TTFields alone (65%) and FOLFOX alone (34%). Similar results were observed for the combined treatment of TTFields and FOLFOX in KATO III cells. Conclusions: The results presented in this work demonstrate that TTFields can be an effective treatment against gastric carcinoma and that the combination with FOLFOX may further enhance treatment efficacy. Based on the above, there is a strong rational to continue exploring the potential of the use of TTFields together with standard of care for the treatment of gastric cancer in the clinical settings. Citation Format: Tali Voloshin, Einav Zeevi, Karnit Gotlib, Rosa S. Schneiderman, Mijal Munster, Yaara Porat, Shiri Davidi, Anna Shteingauz, Noa Kaynan, Moshe Giladi, Eilon D. Kirson, Uri Weinberg, Adrian Kinzel, Yoram Palti. The efficacy of the combined treatment of 150 kHz Tumor Treating Fields (TTFields) and FOLFOX in gastric cancer in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 303.
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