Document Detail


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.
MedLine Citation:
PMID:  14574458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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/m(2) 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.
Authors:
Vania T M Hungria; Maria C Latrilha; Debora G Rodrigues; Sergio P Bydlowski; Carlos S Chiattone; Raul C Maranhão
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-10-22
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  53     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2003-12-05     Completed Date:  2004-02-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  51-60     Citation Subset:  IM    
Affiliation:
Hematology and Hemotherapy Section, Santa Casa Medical School, São Paulo, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating / administration & dosage*,  blood,  therapeutic use
Carmustine / administration & dosage*,  blood,  therapeutic use
Cell Line, Tumor
Cell Survival / drug effects
Cholesterol / administration & dosage*,  blood,  metabolism
Drug Carriers / administration & dosage,  metabolism,  pharmacokinetics
Emulsions
Female
Humans
Lipid Metabolism
Lipids / blood
Male
Middle Aged
Multiple Myeloma / drug therapy,  metabolism*,  pathology
Neoplasm Staging
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Alkylating; 0/Drug Carriers; 0/Emulsions; 0/Lipids; 154-93-8/Carmustine; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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