Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy.
Pegylated liposomal doxorubicin (Doxil, Caelyx) is a formulation of doxorubicin in poly(ethylene glycol)-coated (stealth) liposomes with a prolonged circulation time and unique toxicity profile. We review the preclinical and clinical pharmacology as well as recent clinical data obtained in specific cancer types. Doxil liposomes retain the drug payload during circulation and accumulate preferentially in tissues with increased microvascular permeability, as often is the case of tumors. Doxil toxicity profile is drastically different from that of doxorubicin, and is characterized by dominant and dose-limiting mucocutaneous toxicities, mild myelosuppression, minimal alopecia, and no apparent cardiac toxicity. Although the single maximum tolerated dose (MTD) of Doxil is actually lower than that of conventionally administered doxorubicin, the cumulative MTD dose of Doxil may be substantially greater than that of free doxorubicin. Doxil is probably one of the most active agents in AIDS-related Kaposi's sarcoma and has a definite role in management of recurrent ovarian cancer. The potential of Doxil in the treatment of other cancer types and the opportunities it offers in combination with other drugs and therapeutic modalities are under active investigation.
Gabizon
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Sharet Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. alberto@md2.huji.ac.il
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000505:Alopecia / Q000139:chemically induced; D000707:Anaphylaxis / Q000139:chemically induced; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000139:chemically induced; D001943:Breast Neoplasms / Q000188:drug therapy; D009202:Cardiomyopathies / Q000139:chemically induced; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers; D003875:Drug Eruptions / Q000209:etiology; D004342:Drug Hypersensitivity / Q000209:etiology; D004357:Drug Synergism; D005260:Female; D005544:Forecasting; D006207:Half-Life; D006801:Humans; D007928:Lethal Dose 50; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism; D020714:Maximum Tolerated Dose; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D051381:Rats; D012189:Retrospective Studies; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000209:etiology; D012995:Solubility; D013280:Stomatitis / Q000139:chemically induced; D013535:Suspensions; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D013535:Suspensions; D004317:Doxorubicin