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EC917 Drug Eluting Bead: Future Product Applications Eva Gallardo, MD Medical Manager, Biocompatibles UK EC917 DEB in Glioma: Background • Malignant Gliomas are most frequent primary brain tumours • Total surgical resection is challenging due to infiltrative nature • Median Survival: • Low-grade Glioma: 5 years (most die of progression to high-grade) • High-Grade Glioma: <5% survival at 2 years • Polymer drug release post-resection has improved treatment outcomes (this therapy is under further development) EC917 DEB in Glioma: Methods • Study in glioblastoma rat model to evaluate efficacy of Irinotecan and Doxorubicin Bead • Control Group: 1-3 µL of 100-300 µm beads injected • Dose ranging study: 1-3 µL of loaded 100-300 µm beads injected. Histogical evaluation 12 days post-tumour implant • Survival study: 1 µL of 100-300 µm loaded beads injected. Animal activity and well-being assessed twice daily. Euthanised if low scores or sudden neurological signs. • Histological evaluation: tumour size, histomorphology, bead location and amount, drug distribution EC917 DEB in Glioma: Results • No histological tissue damage found with bland beads • Tumoural citotoxic effect of both drugs with tumour necrosis • Neuronal, glial and capillary cells were also destroyed by doxorubicin (not by irinotecan) EC917 DEB in Glioma: Results P Bead vs Dox Bead 0.0028 P Bead vs Iri Bead 0.0018 EC917 DEB in Glioma: Results • DEB could be a promising new local therapy for glioma • Doxorubin showed the longer survival but with a dose limiting toxicity • Further evaluation is required EC917 DEB in Peritoneal Carcinomatosis: Background • Peritoneal carcinomatosis leading to malignant ascites is a complication of several solid tumors (ovarian, gastric, liver and pancreatic cancers) • Appears in late disease stage – difficult to manage • Is the life-limiting factor and leads to severe complications – bowel obstruction • Symptoms include severe pain and dyspnea EC917 DEB in Peritoneal Carcinomatosis: Methods • Doxorubicin or Mitoxantrone loaded Beads were used in a peritoneal colorectal carcinomatosis mice model (a) 1 mm (b) 1 mm (c) 1 mm • Control Group: direct intraperitoneal injection of unloaded beads at 7, 10 and 12d • Direct intraperitoneal injection of free drug or loaded Bead (single low dose/single high dose/multiple doses) EC917 DEB in Peritoneal Carcinomatosis: Results • Dox and Mitox induced dose-dependent reduction in cell proliferation whether free or delivered by DEB • Free drug was more effective at reducing cell viability over time, although DEB was seen to be most effective at 72h (slow release of the drug) • Multiple free Dox was lethal (Dox and Mitox Bead were well tolerated) EC917 DEB in Peritoneal Carcinomatosis: Results 25 20 20 Mitox DEB 100 Mitox (3) Dox DEB 100 Dox (3) 0 Dox DEB(3) 0 Dox 5 Dox DEB 5 Mitox DEB(3) 10 Mitox 10 15 Mitox DEB 15 Control Body Weight (g) 25 Control Body Weight (g) •Multiple free Mitox administration induced significant weight decrease (Mitox Bead did not) EC917 DEB in Peritoneal Carcinomatosis: Results • Multiple administration of Dox or Mitox DEB was very efficacious in reducing tumor volume • A single administration of Dox or Mitox DEB with 100mg/kg dose was both well tolerated and efficacious 5 Dox DEB 100 Dox (3) Dox DEB(3) Dox Dox DEB 0 20 0 Mitox DEB 100 10 40 Mitox (3) 15 60 Mitox DEB(3) 20 80 Mitox 25 Mitox DEB 30 Control Total Tumor Volume (mm3) 100 Control Total Tumor Volume (mm3) 35 EC917 DEB in Peritoneal Carcinomatosis: Conclusion • IP free drugs had efficacy against tumor cells in vivo, but multiple applications of free drug were lethal or had significant effect on body weight indicating poor tolerability • Single application of high dose, or multiple application of lower dose DEB were well tolerated and had a significant effect on reducing tumor volume • DEB could offer a new treatment for peritoneal carcinomatosis