Clinical studies of liposome-encapsulated doxorubicin.
Initial clinical studies with doxorubicin entrapped in the bilayer of phosphatidylglycerol-rich liposomes were hindered by the avid reticuloendothelial system (RES) uptake and by drug leakage from circulating liposomes. In contrast, recent tests of a doxorubicin formulation of polyethyleneglycol-coated liposomes (Doxil) in cancer patients indicate that the drug pharmacokinetic properties are significantly altered, with a prolonged distribution half-life of approximately 2 days. Plasma fractionation studies show that nearly all the drug measured in plasma is in liposome-encapsulated form. The dose of Doxil has been escalated from 25 to 60 mg/m2. Stomatitis is the most significant toxicity, and skin toxicity, in the form of hand-foot syndrome, may complicate the repeated administration of Doxil. A number of objective antitumor responses in a variety of malignancies have been observed, indicating that Doxil is an active antitumor compound. Polyethyleneglycol-coated liposomes show a distinct advantage over previous liposome formulations directed at the RES and appear to be a promising drug delivery system for doxorubicin.
Gabizon
A
A
Department of Oncology, Hadassah University Hospital, Jerusalem, Israel.
Isacson
R
R
Libson
E
E
Kaufman
B
B
Uziely
B
B
Catane
R
R
Ben-Dor
C G
CG
Rabello
E
E
Cass
Y
Y
Peretz
T
T
D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D004337:Drug Carriers; D007205:Indium Radioisotopes; D008081:Liposomes; D004317:Doxorubicin