Liposomal doxorubicin (Doxil): An effective new treatment for Kaposi's sarcoma in AIDS

James, Nicholas D.; Coker, R J; Tomlinson, David R.; Harris, J.R.; Gompels, Mark; Aj, Pinching; Stewart, J.S.W.

doi:10.1016/s0936-6555(05)80269-9

Cited by 174 publications

(90 citation statements)

References 7 publications

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“…Liposomal formulations of various anticancer drugs are widely used in experimental and clinical oncology with some of them, such as Doxil ™ , becoming drugs of choice under certain conditions (Alberts, et al 2004, James, et al 1994, Tejada-Berges, et al 2002. The use of the liposomal carrier allows for decreased side effects of cancer chemotherapeutics, such as nonspecific toxicity, and for enhanced drug delivery into tumors , Safra, et al 2000.…”

Section: Introductionmentioning

confidence: 99%

Enhanced cytotoxicity of monoclonal anticancer antibody 2C5-modified doxorubicin-loaded PEGylated liposomes against various tumor cell lines

Elbayoumi

Torchilin

2007

European Journal of Pharmaceutical Sciences

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Doxorubicin-loaded long-circulating liposomes (Doxil ™ , ALZA Corp.) were additionally modified with the nucleosome-specific monoclonal antibody 2C5 (mAb 2C5) recognizing a broad variety of tumor cells via the tumor cell surface-bound nucleosomes. These mAb 2C5-modified PEGylated liposomes demonstrated 3-to-8-fold increase in the in vitro binding and internalization by multiple cancer cell lines of diverse origins (murine LLC, 4T1, C26 & human BT-20, MCF-7 and PC3), as shown by flow cytometry and epi and confocal microscopy. As a result, mAb 2C5-modified Doxil ™ demonstrated significantly higher cytotoxicity towards various cancer cells, including those resistant to doxorubicin, than all control preparations. The specific internalization of the mAb 2C5-Doxil ™ into cytosol, along with the nuclear localization of their drug load, inside the target cancer cells were mainly responsible the superior anticancer activity. The IC50 values of mAb 2C5-Doxil ™ with various murine and human cancer cells were 5-to-8-fold lower than those of control doxorubicin-loaded liposomes, Doxil ™ or Doxil ™ modified with a non-specific IgG.

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Section: Introductionmentioning

confidence: 99%

Enhanced cytotoxicity of monoclonal anticancer antibody 2C5-modified doxorubicin-loaded PEGylated liposomes against various tumor cell lines

Elbayoumi

Torchilin

2007

European Journal of Pharmaceutical Sciences

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“…The most important adverse reactions observed in clinical studies were neutropenia (30%-40%), stomatitis (5%-30%), alopecia (up to 10%) and nausea (10%) [1,13,16,28]. In one study, opportunistic infections were observed in 57% of Doxil-treated patients [1].…”

Section: Clinical Efficacy the Results Of Clinical Studies Withmentioning

confidence: 99%

Liposomal formulations of cytotoxic drugs

Janknegt

1996

Support Care Cancer

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Liposomes are microscopic particles of lipid bilayer membrane that enclose aqueous internal compartments. These drug-delivery systems offer a very interesting opportunity for delivering cytotoxic drugs with equal or improved clinical efficacy and reduced toxicity. The most important clinical application of liposomes until now has been the inclusion of amphotericin B. At the same dose level, liposomal amphotericin B is as effective or slightly less effective than the conventional formulation, but much higher dosages, up to 5-7 mg kg-1day-1, can be given with acceptable toxicity. There are three preparations of cytotoxic drugs in an advanced stage of commercial development. Two of these (Doxil and TLD D99) contain doxorubicin and the other (DaunoXome) contains daunorubicin. The cardiac toxicity of the three preparations under clinical evaluation appears to be low in comparison with conventional doxorubicin or daunorubicin. No direct comparisons between the new formulations are available, so it is not yet possible to make any statements concerning their relative efficacy and toxicity. DaunoXome is the only drug that is approved in any country, and is also the best documented. It is too early to make recommendations concerning the place of these drugs in therapy. The marked increase in concentrations at the site of the tumour has yet to lead to increased therapeutic efficacy. These findings need further investigation. The efficacy of liposomal preparations in Kaposi's sarcoma appears to be similar to that of standard therapy and the clinical tolerance is good. Perhaps combination therapy with other cytotoxic agents could result in improved clinical efficacy. Their cost will probably be high in comparison with standard therapies.

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“…Currently, there are a many products in the market and in clinical development for use as anti-cancer drug delivery vehicle (Allen and Cullis 2013) (Table 1). Doxil, a PEGylated liposomal formulation, is the first liposomal product that was approved by the FDA for the treatment of kaposi's sarcoma in AIDS patients (James et al 1994;Barenholz 2012). Doxil (US), or Caelyx (outside-US) is a PEGylated liposomal formulation encapsulating anticancer drug doxorubicin commercialized by Johnson & Johnson.…”

Section: Applications Of Liposomes In Cancermentioning

confidence: 99%