Linked Life Data

1353189

Source:http://linkedlifedata.com/resource/pubmed/id/1353189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8814
pubmed:dateCreated
1992-8-25
pubmed:abstractText
Resistance to chemotherapy in refractory multiple myeloma is frequently associated with expression of multidrug resistance (MDR). In resistant cells, intracellular accumulation of doxorubicin and vincristine does not occur because the MDR-1 gene product, a membrane glycoprotein (PgP), is an energy-dependent efflux pump. Cyclosporin is one of several non-cytotoxic drugs that can block the function of PgP. In a prospective study, we assessed the possibility that cyclosporin could be used clinically to modulate MDR. We studied 21 patients with multiple myeloma; disease had progressed during primary chemotherapy in 6 and was resistant to VAD (vincristine, doxorubicin, dexamethasone) in 15. The patients received cyclosporin by continuous infusion during VAD treatment; there were three cyclosporin dosage groups (5, 7.5, 10 mg/kg daily). Serum cyclosporin concentrations adequate for MDR modulation were reached in all patients receiving 7.5 or 10 mg/kg daily. 47% (7) of the VAD-refractory patients and 48% (10) of the whole group responded to VAD. Before treatment, MDR-1 expression was present in 12 patients. After VAD plus cyclosporin, no MDR-1-positive plasma cells were present in 6 of 8 patients tested. The response rate in MDR-1-positive patients was 58% compared with 33% in all our patients. Toxic effects were mild and reversible and did not include nephrotoxic or serious cardiovascular side-effects. 12 months after the start of treatment, survival was 85%, and disease-free survival at a median of 9 months after the response was 65%. Thus, in multiple myeloma clinical resistance to VAD can be circumvented by cyclosporin, which enables the cytotoxic drugs to eliminate resistant myeloma cells.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0140-6736
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
340
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Modulation of multidrug-resistant multiple myeloma by cyclosporin. The Leukaemia Group of the EORTC and the HOVON.
pubmed:affiliation
Department of Haematology, Erasmus University, University Hospital Dijkzigt, Netherlands, Rotterdam.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't