bevacizumab + floxuridine + irinotecan + leucovorin

This is a combination regimen consisting of four agents: - **Bevacizumab** is a recombinant humanized monoclonal antibody that inhibits angiogenesis by binding to and neutralizing vascular endothelial growth factor A (VEGF-A), thereby preventing the growth of new blood vessels necessary for tumor survival and progression. - **Floxuridine** is an antimetabolite chemotherapeutic agent, structurally related to fluorouracil, that interferes with DNA synthesis by inhibiting thymidylate synthase after conversion to its active metabolites. - **Irinotecan** is a topoisomerase I inhibitor; it prevents DNA from unwinding by stabilizing the complex between topoisomerase I and DNA, leading to double-strand breaks during replication. - **Leucovorin** (folinic acid) enhances the efficacy of fluoropyrimidine drugs like floxuridine by stabilizing their binding to thymidylate synthase. This combination has been studied in metastatic colorectal cancer. The addition of bevacizumab to irinotecan-based regimens (such as those containing fluorouracil or its analogs like floxuridine, plus leucovorin) significantly improves overall survival, progression-free survival, and response rates compared with chemotherapy alone. Bevacizumab’s antiangiogenic effect complements the cytotoxic actions of the other agents[1][2][5].