Doxorubicin, liposome-encapsulated

Pegulated liposomal doxorubicin (Doxil) Liposome encapsulated doxorubicin Ovarian Phase II data... 

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Batist G, Barton J, Chaikin P, Swenson C, Welles L. Myocet (liposome-encapsulated doxorubicin citrate) a new approach in breast cancer therapy. Expert Opin Pharmacother 2002 3 1739-1751. 

Mayer LD, Bally MB, Cullis PR, Wilson SL, Emerman JT. Comparison of free and liposome encapsulated doxorubicin tumor drug uptake and antitumor efficacy in the SCI 15 murine mammary tumor. Cancer Lett 1990 53 183. 

Mickisch GH, Rahman A, Pastan I, et al. Increased effectiveness of liposome-encapsulated doxorubicin in multidrug-resistant-transgenic mice compared with free doxorubicin. J Natl Cancer Inst 1992 84(10) 804-805. 

Long circulating liposomes can exploit the EPR effect to accumulate at sites where pathological reactions occur. For example, the commercial product Doxil (marketed as Caelyx in Europe) consists of smallsized PEGylated liposomes, encapsulating the cytostatic doxorubicin. The resulting long circulation times and small size of the vesicles facilitate their accumulation in tumor tissue via the EPR effect. 

Batist, G., Ramakrishnan, G., and Rao, C. S. (2001), Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer,/. Clin. Oncol., 19,1444-1454. 

Mrozek, E., Rhoades, C. A., Allen, J., Hade,E. M., and Shapiro, C. L. (2005), Phase I trial of liposomal encapsulated doxorubicin (Myocet D-99) and weekly docetaxel in advanced breast cancer patients, Ann. Oncol., 16,1087-1093. 

Harashima, H. Lida, S. Urakami, Y. Tsuchihashi, M. Kiwada, H. Optimization of antitumor effect of liposomally encapsulated doxorubicin based on simulations by pharma-cokinetic/pharmacodynamic modeling. J. Controlled Release 1999, 61 (1-2), 93-106. 

Kanter PM, Bullard GA, Pilkiewicz FG, Mayer LD, Cullis PR, Pavelic ZP. Preclinical toxicology study of liposome encapsulated doxorubicin (TLC D-99) comparison with doxorubicin and empty liposomes in mice and dogs. In Vivo 1993 7(l) 85-95. 

Schuller J, Czejka M, Bandak S, Borow D, Pietrzak C, Marei I, Schernthaner G. Comparison of pharmacokinetics (PK) of free and liposome encapsulated doxorubicin in advanced cancer patients. Onkologie 1995 18(Suppl 2) 184. 

Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, Roman L, Uziely B, Muderspach L, Garcia A, Burnett A, Greco FA, Morrow CP, Paradise LJ, Liang LJ. Phase II study of liposomal doxorubicin in refractory ovarian cancer antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol 1997 15(3) 987-93. 

Harris L, Winer E, Batist G, Rovira D, Navari R, Lee L the TLC D-99 Study Group. Phase III study of TLC D-99 (liposome encapsulated doxorubicin) vs. free doxorubicin in patients with metastatic breast cancer (Abstract 26). Proc Am Soc Clin Oncol 1998 17 A474. 

Shapiro CL, Ervin T, Welles L, Azarnia N, Keating J, Hayes DF. Phase II trial of high-dose liposome-encapsulated doxorubicin with granulocyte colony-stimulating factor in metastatic breast cancer. TLC D-99 Study Group. J Clin Oncol 1999 17(5) 1435-41. 

Harris L, Batist G, Belt R, Rovira D, Navari R, Azarnia N, Welles L, Winer E TLC D-99 Study Group. Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer 2002 94(l) 25-36. 

However, the administration of free doxorubicin often leads to dose-limiting side effects such as cardiotoxicity and myelosu-pression. This toxicity can be reduced by liposomal encapsulation of doxorubicin because of the modified biodistribution of the drug (1). Additionally, the efficiency of the drug is improved due to the passive targeting effect of liposomes. 

Treat, J., Greenspan, A., Forst, D., Sanchez, J. A., Ferrans, V. J., Potkul, L. A., Wooley, P. V., Rahman, A. Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer phase 11 study. J. Natl. Cancer Inst. 1990, 82, 1706-1710. 

Muggia, E. M., Hainsworth, J. D., Jeffers, S., Miller, R, Groshan, S., Tan, M., Roman, L., Uziely, B., Muderspach, L., Garcia, A., Burnett, A., Greco, E A. Phase 11 study of liposomal doxorubicin unrefractory ovarian cancer anti-tumor activity and toxicity modification by liposomal encapsulation. J. Clin. Oncol. 1997, 75, 987—993. 

Rahman A, Treat J, Roh J, et al. A Phase I clinical trail and pharmacokinetic evaluation of liposome-encapsulated doxorubicin. J Clin Oncol 1990 8 1093-1100. 

Eliaz RE, Szoka FC, Jr.. Liposome-encapsulated doxorubicin targeted to CD44 a strategy to kill CD44-overexpressing tumor cells. Cancer Res... 

Gordon, K.B. et al, 1995. Hand-foot syndrome associated with liposome-encapsulated doxorubicin therapy. Cancer, 75(8), 2169-2173. 

Saracchini S, Foltran L, Tuccia F, Bassini A, Sulfaro S, MicheK E, et al. Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide, followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER2 overexpression or amplification. Breast 2013 22(6) 1101-7. 

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