Eradication of peritoneal dissemination in mice by combination therapy using liposome-encapsulated leucovorin with 5-fluorouracil

抄録

Leucovorin (LV)•5-FU combination chemotherapy has been commonly used as adjuvant therapy for gastrointestinal cancer, which induces few side effects and has a high activity. Peritoneal dissemination frequently occurs after surgery and its prevention is essential for improving the prognosis of patients with gastric and colorectal cancer. Before applying LV•5-FU combination therapy for the treatment of peritoneal dissemination, it is necessary to develop the drug delivery systems capable of maintaining optimal concentrations in the peritoneal cavity. We created a slow-release LV microcapsules using liposomes and studied the therapeutic effect of liposome-encapsulated LV (LV liposomes) combined with 5-FU in a mouse model of peritoneal metastasis. LV liposomes demonstrated much more gradual drug release in the peritoneal cavity compared to free LV. In the model of peritoneal dissemination, both averaged tumor weight and the incidence of peritoneal metastasis were lower in the mice treated with LV liposomes and 5-FU than in animals given free LV and 5-FU (p=0.01). In conclusion, LV liposomes combined with 5-FU may be clinically useful for the prevention and treatment of peritoneal dissemination.