Abstract 5361: In vitro results and electric fields simulations suggest Tumor Treating Fields (TTFields) to be an effective treatment against Mesothelioma

Abstract

Abstract Mesothelioma is an aggressive cancer affecting the membrane lining of the lungs and abdomen, and is associated with poor prognosis. Current available treatment options for Mesothelioma, including surgery, radiation therapy and chemotherapy, offer only modest improvement in survival, therefore emphasizing the desperate need for new treatment options. Tumor Treating Fields (TTFields) is a treatment modality based on non-invasive application of low intensity intermediate frequency alternating electric fields that disrupt mitosis. The goal of the present work was to determine whether TTFields in combination with standard of care drugs, could serve as an effective treatment against Mesothelioma. TTFields were applied to Mesothelioma cell cultures using the inovitro system. Cytotoxicity and effect on clonogenicity were determined following 72 hours of TTFields treatment. Combination index (CI) was calculated for the treatment of TTFields with each of the following drugs: Paclitaxel, Cisplatin, Pemetrexed and Vinorelbine. Finite Element Mesh (FEM) simulations were performed using the Sim4life software package (ZMT, Zurich, Switzerland) for the calculations of the electric fields intensities in the mesothelium of a realistic human computational phantom. Frequency titration experiments revealed 150 kHz to be the optimal TTFields frequency for Mesothelioma cell cultures, leading to 69% reduction in the number of cells (p<0.001) and 78% reduction in clonogenicity (p<0.05) as compared to control. The combined treatment of TTFields with Paclitaxel, Cisplatin, Pemetrexed and Vinorelbine resulted in combination index of 0.99, 0.88, 1.29 and 1.13, respectively. FEM simulations demonstrated that electric field intensities within the mesothelium are approximately 2 V/cm RMS which is above the minimal threshold required for TTFields effect. Taken together, these results suggest that combining TTFields therapy with systemic chemotherapy may be an approach that offers enhanced treatment efficacy for Mesothelioma. A clinical study testing the combined efficacy of TTFields Cisplatin and Pemetrexed is under development. Citation Format: Moshe Giladi, Mijal Munster, Roni Blat, Rosa Schneiderman, Yaara Porat, Zeev Bomzon, Noa Urman, Tali Voloshin, Eilon David Kirson, Uri Weinberg, Yoram Palti. In vitro results and electric fields simulations suggest Tumor Treating Fields (TTFields) to be an effective treatment against Mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5361. doi:10.1158/1538-7445.AM2015-5361