P-255 Effects of tumor treating fields (150 kHz) in combination with FOLFOX on gastric cancer cells in vitro

Abstract

Gastric cancer is the third most common cause of cancer mortality worldwide. Long-term survival in gastric cancer remains poor despite advances in systemic therapies. FOLFOX (oxaliplatin, fluorouracil [5-FU], and leucovorin) is an approved chemotherapy regimen for the treatment of gastric cancer. Tumor Treating Fields (TTFields) are an antimitotic, loco-regional anticancer treatment delivered via non-invasive application of low intensity (1-3V/cm), intermediate frequency (100-500 kHz) alternating electrical fields. TTFields target rapidly dividing cancer cells by disrupting microtubules leading to mitotic catastrophe, abnormal chromosome segregation, and apoptosis induction. We investigated the effect of TTFields alone and in combination with FOLFOX in gastric carcinoma cells. Gastric cells (AGS and KATO III) were treated for 72 hours with TTFields (1.1 and 1.7 V/cm, respectively) at frequencies of 100-400 kHz using the Inovitro system. Effectiveness of TTFields alone and in combination with FOLFOX as well as TTFields combined with the individual FOLFOX components (oxaliplatin, 5-FU, or leucovorin) was tested by applying TTFields at the optimal frequency in combination with various drug concentrations. Cell counts, apoptosis induction, clonogenic potential, and overall effect were evaluated. The optimal TTFields frequency that resulted in the greatest cell count reduction (AGS, 55%; KATO III, 52%) was 150 kHz. The clonogenic potential was reduced by >70% in both of the cell lines. TTFields combined with each FOLFOX component (oxaliplatin, 5-FU, or leucovorin) led to a significant reduction in AGS and KATO III cell survival (2-way ANOVA, P < 0.001 for each cell line) versus each treatment alone. In AGS cells, TTFields plus FOLFOX combination treatment led to a further reduction in the overall effect (cytotoxic and clonogenic; 79%) versus TTFields alone (65%) and FOLFOX alone (34%). Similar results were observed in KATO III cells. These results suggest that TTFields at 150 kHz (optimal frequency for gastric cancer cells) show potential as an effective gastric cancer treatment. Combining TTFields with standard-of-care chemotherapy may further enhance clinical efficacy in gastric cancer. TTFields (150 kHz) concomitant with XELOX (oxaliplatin/capecitabine) as the first-line treatment is currently under investigation in a phase 2 trial.