Hepatic arterial infusion in the treatment of liver metastases with PEG liposomes in combination with degradable starch microspheres (DSM) increases tumor 5-FU concentration. an animal study in CC-531 liver tumor-bearing rats.

UNLABELLED: The regional application of cytostatics in liver metastases leads to increased concentrations in the tumor tissue. The effect of flow retardation by temporary occlusion and drug targeting with liposome encapsulation (PEG liposomes) on tumor 5-fluorouracil (5-FU) concentrations was investigated. MATERIALS AND METHODS: Tumor-bearing rats were submitted to i.v. or intraarterial (i.a.) therapy with liposome-encapsulated or non-encapsulated 5-FU. The i.a. groups were additionally treated with or without Spherex® degradable starch microspheres (DSM). The tumor 5-FU concentrations were determined by high-performance liquid chromatography (HPLC) as area under the curve (AUC). RESULTS: A comparison with i.v. in administered 5-FU yielded the following increases tumor concentrations: 5-FU-PEG liposomes i.v. 27-fold, 5-FU i.a. 19-fold, 5-FU i.a. + DSM 1760-fold, 5-FU-PEG liposomes i.a. 110-fold, 5-FU-PEG liposomes i.a. + DSM 7665-fold. CONCLUSION: Liver intratumoral 5-FU concentration increases to >7,500 times that following i.v. administration by a combination of regional administration via the hepatic artery with temporary embolization by DSM and drug targeting by liposome-encapsulated 5-FU.