Regorafenib antitumor activity alone and in combination with radio or chemotherapy in preclinical models of pediatric solid tumors.

10049 Background: Angiogenesis plays a pivotal role in tumor growth and metastatic spread in children. High VEGF expression is correlated with invasion, metastases and risk for recurrence. In several pediatric tumors, angiogenesis is further driven by PDGFR and FGFR signaling. We evaluated the novel potent oral multikinase inhibitor regorafenib (BAY-73-4506) against pediatric cell lines and xenografts. Methods: Inhibition of cell proliferation and migration was explored in vitro against the Innovative Therapies for Children with Cancer (ITCC) cell line panel by MTS assay and against neuroblastoma cells by phase-contrast with Incucyte. In vivo, athymic mice bearing subcutaneous PDGFRA gene amplified IGRG93 glioma (derived from an adult patient) and IGRM57 medulloblastoma, and orthotopic IGR-N91-Luc neuroblastoma xenografts were treated with regorafenib at 10 or 30 mg/kg orally during at least 21 days alone or in combination with irradiation or irinotecan. Results: Regorafenib inhibited cell proliferation i...