Targeted Osmotic Lysis Emergency Use Treatment of a Patient with Aggressive, Late‐stage Cervical Cancer

Abstract

Targeted osmotic lysis (TOL) of cancers takes advantage of the overexpression of voltage-gated sodium channels (VGSCs) in aggressive carcinomas by stimulating VGSCs while simultaneously blocking Na+,K+-ATPase (sodium pumps) with a cardiac glycoside drug. The increase in intracellular [Na+] causes water to enter the cells inducing an osmotic lysis of only the cells that overexpress VGSCs. Emergency Use of TOL was requested by a treating oncologist in the hope of helping a 46 y/o patient with end-stage IIB cervical carcinoma measuring 12.2 × 9.9 × 9.4 cm, 27 days prior to treatment with TOL. Having failed radiation and chemotherapy with pembrolizumab, paclitaxel, carboplatin and bevacizumab, her anticipated life expectancy was less than 2 weeks. Immunohistofluorescenc analysis of tissue taken from the tumor revealed that the cancer sufficiently overexpressed VGSCs relative to stromal cells to anticipate a favorable response to TOL treatment. Necessary ethics, IRB and legal approvals for Emergency Use of TOL were obtained and informed consent was obtained from the patient. She then received daily oral 0.25 mg doses of digoxin for 4 days to achieve a therapeutic blood level (0.50-1.50 ng/ml). To maintain steady-state pharmacokinetics, a 0.25 mg dose of digoxin was administered prior to each of the two 2-hr periods of stimulation with uniform pulsed electric fields (18 V/m, 10 ms positive/negative square wave, 15 ms interstimulus interval) using a custom built coaxial ring device. Treatment was administered on 2 successive days. Her life expectancy was less than 3 days at the time of first treatment. Due to the large tumor size, the patient also received 1 L of normal saline pre- and post-treatment and 300 mg of allopurinol to reduce the risk of tumor lysis syndrome. The patient experienced no ill effects from the treatment. CT scans were repeated 3 and 18 days post-treatment with TOL. The sizes and tissue densities of the tumor was measured in the post-treatment scans and compared to measurements taken from the pre-treatment scan. Tumor size increased 36% from baseline at 3 days and again increased another 40% 15 days later. By contrast, tumor density decreased from 70 HU at baseline to 56 HU and 47 HU, respectively, post-treatment indicative of the large hypodense regions observed on the scans. The patient survived 9 weeks post-treatment with improved quality of life. This case is evidence that TOL is a promising treatment for aggressive, late-stage carcinomas and warrants further study.