caa a22 4500 467948178 CHVBK 20180405193739.0 cr unu---uuuuu 170328e20040101xx s 000 0 eng 10.1007/s00280-003-0692-y doi (NATIONALLICENCE)springer-10.1007/s00280-003-0692-y (NATIONALLICENCE)springer-10.1007/BF02665353 Metabolism of a cholesterol-rich microemulsion (LDE) in patients with multiple myeloma and a preliminary clinical study of LDE as a drug vehicle for the treatment of the disease [Elektronische Daten] [Vania Hungria, Maria Latrilha, Debora Rodrigues, Sergio Bydlowski, Carlos Chiattone, Raul Maranhão] Purpose: Previously we have shown that cholesterol-rich microemulsions that bind to LDL receptors have the ability to concentrate in acute myeloid leukemia cells and in ovarian and breast carcinomas. Thus, LDE may be used as a vehicle for drugs directed against neoplastic cells. Indeed, we subsequently showed that when carmustine is associated with LDE the toxicity of the drug is significantly reduced in patients with advanced cancers. The aim of the present study was to verify whether LDE may be taken up by multiple myeloma cells and whether patients with multiple myeloma respond to treatment with LDE associated with carmustine. Methods: A total of 131 consecutive volunteer patients with recently diagnosed multiple myeloma classified as clinical stage IIIA had their plasma lipid profile determined. LDE plasma kinetics were performed in 14 of them. Cell uptake of LDE and the cytotoxicity of carmustine associated with the emulsion were evaluated in a multiple myeloma cell line. A pharmacokinetic study of LDE-carmustine was performed in three patients. Finally, an exploratory clinical study of LDE-carmustine (carmustine dose 180 mg/m2 body surface every 4 weeks) was performed in seven untreated multiple myeloma patients. Results: LDL cholesterol was lower in the 131 multiple myeloma patients than in healthy controls and the fractional clearance rate (FCR, in units per minute) in the 14 multiple myeloma patients was twice that in 14 paired healthy control subjects. Moreover, entry of LDE into multiple myeloma cells was shown to be mediated by LDL receptors. Taken together, these findings indicate that LDE may target multiple myeloma. The exploratory clinical study showed that gammaglobulin decreased by 10-70% (mean 36%) after three cycles and by 25-75% (mean 44%) after six cycles. Furthermore, there was amelioration of symptoms in all patients. Cholesterol concentrations increased after treatment, suggesting that the treatment resulted in at least partial destruction of neoplastic cells with receptor upregulation. Side effects of the treatment were negligible. Conclusions: Because it targets multiple myeloma and, when associated with an antineoplastic agent, produces therapeutic responses in patients with fewer side effects, LDE has the potential for use as a drug vehicle in the treatment of the disease. Springer-Verlag, 2003 Emulsions nationallicence Cancer chemotherapy nationallicence Multiple myeloma nationallicence Carmustine nationallicence Cholesterol nationallicence Low-density lipoprotein (LDL) receptors nationallicence Drug targeting nationallicence Hungria Vania Hematology and Hemotherapy Section, Santa Casa Medical School, São Paulo, Brazil aut Latrilha Maria Lipid Metabolism Laboratory, Heart Institute (INCOR), University of São Paulo Medical School Hospital, Av. Dr. Eneas de Carvalho Aguiar 44, 1 subsolo, 05403-000, São Paulo, Brazil aut Rodrigues Debora Lipid Metabolism Laboratory, Heart Institute (INCOR), University of São Paulo Medical School Hospital, Av. Dr. Eneas de Carvalho Aguiar 44, 1 subsolo, 05403-000, São Paulo, Brazil aut Bydlowski Sergio Department of Hematology, University of São Paulo Medical School Hospital, São Paulo, Brazil aut Chiattone Carlos Hematology and Hemotherapy Section, Santa Casa Medical School, São Paulo, Brazil aut Maranhão Raul Lipid Metabolism Laboratory, Heart Institute (INCOR), University of São Paulo Medical School Hospital, Av. Dr. Eneas de Carvalho Aguiar 44, 1 subsolo, 05403-000, São Paulo, Brazil aut Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 51-60 0344-5704 53:1<51 2004 53 280 https://doi.org/10.1007/s00280-003-0692-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00280-003-0692-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hungria Vania Hematology and Hemotherapy Section, Santa Casa Medical School, São Paulo, Brazil aut NATIONALLICENCE 700 1- Latrilha Maria Lipid Metabolism Laboratory, Heart Institute (INCOR), University of São Paulo Medical School Hospital, Av. Dr. Eneas de Carvalho Aguiar 44, 1 subsolo, 05403-000, São Paulo, Brazil aut NATIONALLICENCE 700 1- Rodrigues Debora Lipid Metabolism Laboratory, Heart Institute (INCOR), University of São Paulo Medical School Hospital, Av. Dr. Eneas de Carvalho Aguiar 44, 1 subsolo, 05403-000, São Paulo, Brazil aut NATIONALLICENCE 700 1- Bydlowski Sergio Department of Hematology, University of São Paulo Medical School Hospital, São Paulo, Brazil aut NATIONALLICENCE 700 1- Chiattone Carlos Hematology and Hemotherapy Section, Santa Casa Medical School, São Paulo, Brazil aut NATIONALLICENCE 700 1- Maranhão Raul Lipid Metabolism Laboratory, Heart Institute (INCOR), University of São Paulo Medical School Hospital, Av. Dr. Eneas de Carvalho Aguiar 44, 1 subsolo, 05403-000, São Paulo, Brazil aut NATIONALLICENCE 773 0- Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 51-60 0344-5704 53:1<51 2004 53 280 NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02665353 text/html Onlinezugriff via DOI Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE NATIONALLICENCE NL-springer