ChemoSeed®: A Novel Implantable Device for the Treatment of High Grade Gliomas

Abstract

Abstract AIMS The treatment of high grade gliomas (HGGs) is extremely toxic, while offering a dismal prognosis of 15 months survival. Irinotecan (IRN) is a second-line therapy due to its dose-limiting toxicities when delivered systemically. The aim of this research is to formulate IRN into ChemoSeed for local administration to the resection margin of HGGs and evaluate it for toxicity and efficacy in a Patient-Derived Xenograft mouse resection model. METHOD 30 and 40% w/w IRN-loaded ChemoSeeds were manufactured using hot melt extrusion and were subsequently implanted into the resection cavity of HGG tumour bearing mice. RESULTS The 30% w/w IRN-loaded ChemoSeeds showed moderate local toxicity two days after implantation, which diminished by day 4. The 40% w/w IRN-loaded ChemoSeeds showed signs of moderate local toxicity up to six days post implantation, diminishing by day 8 with mild toxicity returning at day 14. Histopathology of the implantation site showed signs of the onset of necrosis at day 45 and 14 for the 30% and 40% w/w IRN-loaded ChemoSeeds. Hematological analysis and clinical chemistry showed no signs of serious systemic toxicity for either the 30 or 40% w/w IRN-loaded ChemoSeeds. The 30% w/w IRN-loaded ChemoSeeds had an 80% survival at day 148, with no sign of tumour recurrence, while the 40% w/w group showed signs of tumour recurrence at day 21, with all mice dead by day 70. CONCLUSION This study demonstrates that the 30% w/w IRN-loaded ChemoSeeds are a promising novel treatment for HGGs that could be quickly translated into the clinic.