Efficacy of tumor treatment field (TTF) therapy alone and in combination with chemotherapyin pancreatic cancer preclinical models.

Abstract

e14616 Background: TTF therapy is a novel, non-invasive treatment modality for solid tumors and was recently approved by the FDA for recurrent glioblastoma. It utilizes alternating electric fields to inhibit tumor growth, by mitotic spindle disruption and destruction of plasma membrane integrity during cytokinesis. TTF inhibits the growth of many solid tumor cell lines in vitro and in vivo. The optimal treatment for pancreas cancer remains elusive, thus we sought to evaluate the efficacy of TTF in pre-clinical pancreatic cancer models. Methods: Cultures of hamster and human pancreatic adenocarcinoma cell lines (PC1-0 and AsPC-1, respectively) were treated with TTF (frequencies ranging from 75 to 300 kHz), using two pairs of perpendicularly oriented insulated transducer arrays. Once determining optimal frequency, TTF was combined with chemotherapy (gemcitabine or 5-Fluorouracil, 5-FU). Hamsters bearing syngeneic, orthotopic pancreatic tumors were treated with either TTF alone or in combination with gemcitabine or 5-FU. Results: TTF treatment had significant inhibitory effect on proliferation of pancreatic cancer cultures. The maximal inhibitory effect for PC1-0 and ASPC-1 was observed when TTF frequencies of 100 and 150 kHz were applied (respectively). The application of TTF to cultures treated with either gemcitabine or 5-FU resulted in an additive inhibitory effect. In-vivo, TTF therapy, either alone or in combination with chemotherapy, resulted in a significant decrease in tumor weight and volume. Compared to chemotherapy alone, TTF increased tumor response to both gemcitabine and 5-FU. Histological analysis demonstrated higher mitotic index in TTF-treated tumors, consistent with the mitotic arrest previously shown in TTF treated cultures. Conclusions: TTF therapy demonstrated efficacy in pancreatic adenocarcinoma in both in vitro and in vivo models. These results support the evaluation of this novel treatment modality in combination with standard chemotherapy in pancreatic cancer patients. A pilot study is in development to test the clinical benefit of combined TTF and gemcitabine in patients with advanced pancreatic adenocarcinoma.