Hepatic arterial infusion (HAI) with PEGylated liposomes containing 5-FU improves tumor control of liver metastases in a rat model

Invest New Drugs. 2012 Jun;30(3):927-35. doi: 10.1007/s10637-011-9646-0. Epub 2011 Mar 1.

Abstract

Purpose: To investigate the cytostatic effect of 5-fluorouracil (5-FU) encapsulated in polyethylene glycol (PEG) liposomes with or without degradable starch microspheres (DSM) in a long-term trial using a rat liver tumor model.

Materials and methods: The cytostatics were applied once either as a hepatic arterial infusion (HAI) or were systemically infused via the tail vein. Seven groups were compared with respect to tumor growth and survival times: 5-FU HAI (group I), 5-FU + DSM HAI (group II), PEG-5-FU HAI (group III), PEG-5-FU + DSM HAI (group IV), NaCl HAI (group V), 5-FU i.v. (group VI), and PEG-5-FU i.v. (group VII).

Results: Seven and 14 days after treatment in groups III and IV, only group IV had significantly inhibited tumor growth on day 21 compared to the groups treated intravenously. On day 28, none of the animals from the intravenously treated groups were still alive compared to a significantly longer survival time of 6 and 8 weeks in groups III and IV.

Conclusion: Locoregional therapy with 5-fluorouracil encapsulated in PEGylated liposomes may further improve the treatment success with longer-lasting tumor regression and prolonged survival times.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Cell Line, Tumor
  • Fluorouracil / administration & dosage*
  • Hepatic Artery
  • Infusions, Intra-Arterial
  • Liposomes
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Polyethylene Glycols / administration & dosage
  • Rats
  • Tumor Burden / drug effects

Substances

  • Antimetabolites, Antineoplastic
  • Liposomes
  • Polyethylene Glycols
  • Fluorouracil