Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours

Drugs. 1997;54 Suppl 4:15-21. doi: 10.2165/00003495-199700544-00005.

Abstract

Polyethylene glycol (PEG)-coated (pegylated; Stealth) liposomes are stable, long-circulating drug carriers useful for delivering doxorubicin to the sites of solid tumours. Compared with conventional liposomes, pegylated liposomes are less extensively taken up by cells of the reticuloendothelial system (RES) and have a reduced tendency to leak drug while in circulation. The pharmacokinetics of PEG-liposome encapsulated doxorubicin are characterised by an extremely long circulating half-life, slow plasma clearance and a reduced volume of distribution compared with conventional liposomal doxorubicin or free doxorubicin. The long circulation and ability of pegylated liposomes to extravasate through 'leaky' tumour vasculature results in localisation of doxorubicin in tumour tissue. In a number of animal and human tumours, including breast, prostate, pancreatic and ovarian xenografts, pegylated liposomal doxorubicin produced higher intratumoural drug concentrations and better therapeutic responses than equivalent doses of conventional (nonpegylated)-liposome encapsulated doxorubicin or free doxorubicin. Low peak plasma concentrations of free doxorubicin after administration of pegylated liposomal doxorubicin and the reduced tendency of the liposomal drug to accumulate in myocardium suggest that a reduction in cardiac toxicity compared with free doxorubicin may be observed. Thus, the rationale for the use of pegylated liposomal doxorubicin in solid tumours may be summarised as follows: change in the toxicity profile with a decrease in acute adverse effects (such as nausea and vomiting) and reduced incidence of alopecia, greater activity in highly angiogenic tumours (such as Kaposi's sarcoma) and effective treatment of tumours moderately sensitive to doxorubicin (such as breast and ovarian carcinomas), with the possibility of increased tumour response because of enhanced drug accumulation. In addition, although no comparative study yet exists, there is a suggestion from early human studies with pegylated liposomal doxorubicin that cardiotoxicity may be reduced compared with the free drug.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Doxorubicin / administration & dosage*
  • Doxorubicin / adverse effects
  • Doxorubicin / pharmacokinetics
  • Drug Carriers*
  • Drug Delivery Systems
  • Heart Diseases / chemically induced
  • Humans
  • Liposomes / chemistry*
  • Neoplasms / drug therapy*
  • Polyethylene Glycols*

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Liposomes
  • Polyethylene Glycols
  • Doxorubicin