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dc.contributor.authorThompson, JF
dc.contributor.authorSiebert, GA
dc.contributor.authorAnissimov, YG
dc.contributor.authorSmithers, BM
dc.contributor.authorDoubrovsky, A
dc.contributor.authorAnderson, CD
dc.contributor.authorRoberts, MS
dc.date.accessioned2017-09-06T03:28:01Z
dc.date.available2017-09-06T03:28:01Z
dc.date.issued2001
dc.date.modified2014-05-09T03:00:16Z
dc.identifier.issn0007-0920
dc.identifier.doi10.1054/bjoc.2001.1902
dc.identifier.urihttp://hdl.handle.net/10072/59078
dc.description.abstractThis study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chemotherapy by Isolated Limb Infusion (ILI). 19 patients undergoing ILI for treatment of various limb malignancies were monitored for intra-operative melphalan concentrations in plasma and, using microdialysis, in subcutaneous and tumour tissues. Peak and mean concentrations of melphalan were significantly higher in plasma than in subcutaneous or tumour microdialysate. There was no significant difference between drug peak and mean concentrations in interstitial and tumour tissue, indicating that there was no preferential uptake of melphalan into the tumours. The time course of melphalan in the microdialysate could be described by a pharmacokinetic model which assumed melphalan distributed from the plasma into the interstitial space. The model also accounted for the vascular dispersion of melphalan in the limb. Tumour response in the whole group to treatment was partial response: 53.8% (n= 7); complete response: 33.3% (n= 5); no response: 6.7% (n= 1). There was a significant association between tumour response and melphalan concentrations measured over time in subcutaneous microdialysate (P< 0.01). No significant relationship existed between the severity of toxic reactions in the limb or peak plasma creatine phosphokinase levels and peak melphalan microdialysate or plasma concentrations. It is concluded that microdialysis is a technique well suited for measuring concentrations of cytotoxic drug during ILI. The possibility of predicting actual concentrations of cytotoxic drug in the limb during ILI using our model opens an opportunity for improved drug dose calculation. The combination of predicting tissue concentrations and monitoring in microdialysate of subcutaneous tissue could help optimise ILI with regard to post-operative limb morbidity and tumour response.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom157
dc.relation.ispartofpageto165
dc.relation.ispartofjournalBritish Journal of Cancer
dc.relation.ispartofvolume85
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchPublic Health and Health Services
dc.subject.fieldofresearchcode1112
dc.subject.fieldofresearchcode1117
dc.titleMicrodialysis and response during regional chemotherapy by isolated limb infusion of melphalan for limb malignancies.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codec1x
dcterms.licensehttp://creativecommons.org/licenses/by-nc-sa/3.0/
gro.facultyFaculty of Science
gro.rights.copyright© The Author(s) 2001. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
gro.date.issued2001
gro.hasfulltextFull Text
gro.griffith.authorAnissimov, Yuri G.


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