pazopanib + evofosfamide

Pazopanib + evofosfamide is a combination of two investigational anti-cancer agents. Pazopanib is an oral small molecule multi-targeted tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor 1 (VEGFR-1), vascular endothelial growth factor receptor 2 (VEGFR-2), vascular endothelial growth factor receptor 3 (VEGFR-3), platelet-derived growth factor receptor alpha, platelet-derived growth factor receptor beta, and c-kit. This inhibition disrupts angiogenesis—the formation of new blood vessels—thereby starving tumors of nutrients needed for growth[6][8]. Pazopanib is approved for advanced renal cell carcinoma and soft tissue sarcoma[1][2][5]. Evofosfamide is a hypoxia-activated prodrug designed to target the low-oxygen (hypoxic) regions within solid tumors. Under hypoxic conditions, it releases bromo-isophosphoramide mustard (Br-IPM), a DNA crosslinking agent that induces cell death by preventing DNA replication in cancer cells[3]. Evofosfamide remains largely inactive under normal oxygen levels but becomes cytotoxic in tumor hypoxia. The combination aims to exploit complementary mechanisms—pazopanib's antiangiogenic effects may increase tumor hypoxia, thereby enhancing the activation and efficacy of evofosfamide.