Journal
CANCER INVESTIGATION
Volume 19, Issue 4, Pages 424-436Publisher
TAYLOR & FRANCIS INC
DOI: 10.1081/CNV-100103136
Keywords
animal rumors; anthracyclines; chemotherapy; doxorubicin; drug delivery; human cancer; liposomes; pharmacokinetics; stealth; targeting.; therapeutics; toxicity
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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 recant 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 myelosupression, 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 Lire under active investigation.
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