Abstract 5365: Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo

Abstract

Abstract Tumor Treating Fields (TTFields) are low intensity intermediate frequency alternating electric fields that disrupt mitosis. Our previous in vitro studies suggest that ovarian cancer cells are highly sensitive to TTFields treatment. The goal of the present study was to evaluate the efficacy of the combined treatment of TTFields and paclitaxel against ovarian cancer cells in vitro and in vivo. For in vitro studies, TTFields (1.75 V/cm) were applied for 72 hours using the inovitro system. The in vivo efficacy of the combined treatment was tested in C57Bl/6 mice, orthotopically injected with MOSE-L FFL luciferase positive cells. Finite Element Mesh (FEM) simulations were performed using the Sim4life software package (ZMT, Zurich, Switzerland) for the calculations of the electric fields intensities around the ovaries. Our results demonstrate that in vitro application of 200 kHz TTFields led to a significant reduction in both the number of viable cells (44.6%) and the clonogenic potential (23.8%) as compared to untreated cells (p<0.001). Further reduction in the number of viable cells was achieved when TTFields were combined with paclitaxel. In vivo, the combined treatment of TTFields and Paclitaxel led to a significant reduction in tumor luminescence (40%, p<0.01) and in the tumor weight (55%, p<0.05) as compared to untreated tumor bearing mice. FEM simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a real human anatomy model are about 1 and 2 V/cm RMS which is above the minimal threshold required for TTFields response. Taken together these results demonstrate that the combined treatment of TTFields and paclitaxel could serve as an effective treatment against ovarian cancer. A clinical trial testing the efficacy of the combined modalities is now underway. Citation Format: Mijal Munster, Christopher P. Roberts, Eva M. Schmelz, Moshe Giladi, Roni Blat, Rosa S. Schneiderman, Yaara Porat, Zeev Bomzon, Noa Urman, Aviran Itzhaki, Tali Voloshin Sela, Shay Cahal, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo. [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 5365. doi:10.1158/1538-7445.AM2015-5365