arfolitixorin + bevacizumab

Arfolitixorin + bevacizumab is an investigational drug combination evaluated for the first-line treatment of metastatic colorectal cancer (mCRC). Arfolitixorin is a stabilized, biologically active, pure form of folate (6R-MTHF, the active metabolite of folate) that directly enhances the cytotoxicity of 5-fluorouracil (5-FU) by stabilizing the binding of the 5-FU metabolite (5-FdUMP) to thymidylate synthase, thereby halting DNA synthesis in tumor cells. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A), thereby blocking angiogenesis (formation of new blood vessels necessary for tumor growth). The combination (along with 5-FU and oxaliplatin) has been investigated in phase I/II and phase III trials for mCRC. The phase III AGENT study compared arfolitixorin versus leucovorin (the current folate standard) plus 5-FU, oxaliplatin, and bevacizumab. While the combination was well tolerated, the combination with arfolitixorin at 120 mg/m^2^ did not show superiority in objective response rate over leucovorin in this setting. However, higher doses of arfolitixorin may warrant further research[3][6][8].