Abstract 1806: Local chemotherapy and chemoradiation therapy using INCeRT brachytherapy implants in cancer models

Abstract Systemic chemotherapy which is often used in combination with radiation therapy in the treatment of prostate cancer, often leads to severe systemic toxicities. Localized chemotherapy has the potential of delivering a high and effective dose directly to the tumor while minimizing adverse toxicities to healthy tissue. An efficient local delivery system should be able to deliver the therapeutic drug at the diseased site in a slow and sustained manner with minimal systemic toxicity. We have fabricated an Implantable Nanoplatform for Chemo-Radiation Therapy (INCeRT) spacer that can deliver planned, localized, and sustained delivery of a chemotherapeutic and imaging agent. Delivery of this new chemotherapy modality can leverage technology used in a routine clinical brachytherapy procedure that uses image guidance to insert radioactive seeds into the prostate using thin needles. The current procedure uses inert plastic spacers with no therapeutic impact to guide the spatial delivery of the radioactive seeds. This work presents the fabrication, characterization, and therapeutic benefit of a docetaxel loaded spacer in the treatment of prostate-tumored mice. First, INCeRT spacers were fabricated and characterized using optical imaging to track free dye and multi-sized fluorescent silica nanoparticles from spacers in vivo to optimize the temporal and spatial properties of diffusion distribution from a degrading biocompatible polymer matrix. In vivo optical imaging of spacers doped with free dye demonstrates a spatial and temporal release profile appropriate for sustained localized exposure of a chemotherapeutic during the course of brachytherapy. The optimized spacer were loaded with chemotherapeutics and inserted intratumorally for efficacy and toxicity of the localized chemotherapy in comparison to the standard systemic dosing. The in vivo results suggest that local chemotherapy is not only feasible, but as effective as current treatment options. An intratumoral free docetaxel spacer showed to be as effective as a one-time equivalent dose of the clinically used systemic taxotere without the associated adverse toxicities. This new localized chemo-treatment shows great potential for increasing tumor regression while decreasing systemic toxicity. Further experiments for studying the combined chemo-radiation therapy are underway. This demonstrates that local chemotherapy and chemo-radiation therapy has the potential to be a superior treatment option to current chemo-treatments. This work was supported partially by ARMY/ W81XWH-12-1-0154, NSF-DGE-0965843, HHS/1U54CA151881 CORE1 and a seed grant from the BWH Biomedical Research Institute. Citation Format: Rajiv Kumar, Jodi Belz, Houari Korideck, Robert Cormack, Mike Makrigiorgos, Srinivas Sridhar. Local chemotherapy and chemoradiation therapy using INCeRT brachytherapy implants in cancer models. [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 1806. doi:10.1158/1538-7445.AM2015-1806