Definition

A liposomal formulation composed of a combination of two antineoplastic agents, the hydrochloride (HCl) salt form of irinotecan, a semisynthetic camptothecin analogue, and floxuridine, a fluorinated pyrimidine monophosphate analogue of 5-fluoro-2′-deoxyuridine-5′-phosphate (FUDR-MP), with potential antineoplastic activity. Upon administration of irinotecan HCl/floxuridine liposome LY01616, irinotecan selectively stabilizes topoisomerase I-DNA covalent complexes during the S phase of the cell cycle, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery. Floxuridine, as an antimetabolite, inhibits thymidylate synthase, resulting in disruption of DNA synthesis and cytotoxicity. This agent is also metabolized to fluorouracil and other metabolites that can be incorporated into RNA and inhibit the utilization of preformed uracil in RNA synthesis. Liposome encapsulation of two antineoplastic agents at an optimal ratio can promote efficient drug delivery, improve efficacy and increase the synergistic effect.