CHEMOIMMUNOTHERAPY OF MURINE LIVER METASTASES WITH 5-FLUOROURACIL IN COMBINATION WITH LIPOSOME-ENCAPSULATED MURAMYL DIPEPTIDE

The therapeutic effect of a combination of liposomal muramyl dipeptide (MDP) and 5-fluorouracil (5FU) was studied in a murine tumor model of hepatic metastases of the tumor cell line C26, a colon adenocarcinoma. Liposomal MDP (250 mug/kg body wt) and a low, nontoxic, dose of 5FU (10 mg/kg body wt) were mixed and administered during 6 consecutive days once daily, three times i.v. and three times i.p. Treatment was initiated 4 days after intrasplenic tumor cell injection. The combination of liposomal MDP and 5FU significantly reduced the number of liver metastases and the total tumor load in the liver. Liver weights of tumor-bearing mice treated with the combination were significantly lower than the liverweights of control mice (p < 0.005) and of mice treated with 5FU alone (p < 0.02) or liposomal MDP alone (p < 0.05). Liposomal MDP and 5FU, when given as single treatment modalities, had no significant effect on the number of metastases and liver weight. These results show that liposomal MDP can enhance the therapeutic effect of 5FU for the treatment of liver metastases.