Palliative treatment of obstructive esophageal cancer by vascular targeted photodynamic therapy (VTP): Preclinical study in orthotopic rat model.

Abstract

59 Background: Vascular targeted photodynamic therapy (VTP) based on local sensitization of circulating WST11 (Pd-bacteriochlorophyll), enables effective focal ablation of solid tumors. WST11 clears from the circulation with t1/2 ~40 min (in humans) and does not accumulate in tissues which assures high level of safety and minimal adverse effects. Here we evaluate WST11-VTP for the treatment of obstructive esophageal cancer aiming at developing clinically relevant protocol. Methods: Using endoscopy guided procedure rat esophageal cancer cells (JA) were implanted in the mid esophagus. Following intravenous infusion of WST11, established tumors were illuminated by cylindrical fiber using the same endoscope sleeve. Safety and efficacy were evaluated by monitoring animal weight shift and histology of treated esophageal tissues. Treated animals included control (light/no WST11 or WST11/no light), WST11-VTP and WST11-VTP following treatment with bevacizumab at day -3. Results: WST11-VTP on esophageal tissues resulted in coagulative necrosis of the tumor graft and prolonged survival as evident by Kaplan—Meyer curves. The impact was confined to the illuminated site without signs of perforation or death. Following Bevacizumab, WST11-VTP showed similar results while control groups showed no effect. All treated animals started to regain weight at day 7 after VTP. Esophageal tissue and function was completely restored. Conclusions: WST11-VTP could be safely applied for the treatment of esophageal tumors, with only transient and mild adverse effect that are not affected by previous, clinically relevant treatment such as Bevacizumab application. Importantly, VTP effectively eradicated established esophageal tumors and could be translated into a clinical treatment protocol.