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  5. Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά) - ΙΑΤ
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Please use this identifier to cite or link to this item: https://olympias.lib.uoi.gr/jspui/handle/123456789/19890
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dc.contributor.authorMcLeod, H. L.en
dc.contributor.authorMurray, L. S.en
dc.contributor.authorWanders, J.en
dc.contributor.authorSetanoians, A.en
dc.contributor.authorGraham, M. A.en
dc.contributor.authorPavlidis, N.en
dc.contributor.authorHeinrich, B.en
dc.contributor.authorten Bokkel Huinink, W. W.en
dc.contributor.authorWagener, D. J.en
dc.contributor.authorAamdal, S.en
dc.contributor.authorVerweij, J.en
dc.date.accessioned2015-11-24T19:03:22Z-
dc.date.available2015-11-24T19:03:22Z-
dc.identifier.issn0007-0920-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19890-
dc.rightsDefault Licence-
dc.subjectAntibiotics, Antineoplastic/administration & dosage/pharmacokinetics/*therapeuticen
dc.subjectuseen
dc.subjectArea Under Curveen
dc.subjectBreast Neoplasms/*drug therapyen
dc.subjectCarcinoma, Non-Small-Cell Lung/*drug therapyen
dc.subjectFemaleen
dc.subjectHead and Neck Neoplasms/*drug therapyen
dc.subjectHumansen
dc.subjectInjections, Intravenousen
dc.subjectLactones/administration & dosage/pharmacokinetics/therapeutic useen
dc.subjectLung Neoplasms/*drug therapyen
dc.subjectMacrolidesen
dc.subjectMaleen
dc.subjectMelanoma/*drug therapyen
dc.subjectTreatment Outcomeen
dc.titleMulticentre phase II pharmacological evaluation of rhizoxin. Eortc early clinical studies (ECSG)/pharmacology and molecular mechanisms (PAMM) groupsen
heal.typejournalArticle-
heal.type.enJournal articleen
heal.type.elΆρθρο Περιοδικούel
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/8980394-
heal.identifier.secondaryhttp://www.nature.com/bjc/journal/v74/n12/pdf/bjc1996657a.pdf-
heal.languageen-
heal.accesscampus-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.publicationDate1996-
heal.abstractRhizoxin is a macrocyclic lactone compound that binds to tubulin and inhibits microtubule assembly. Rhizoxin demonstrated preclinical anti-tumour activity against a variety of human tumour cell lines and xenograft models. Phase I evaluation found a maximum tolerated rhizoxin dose of 2.6 mg m-2, with reversible, but dose-limiting, mucositis, leucopenia and diarrhoea. Clinical trials were then initiated by the EORTC ECSG in melanoma, breast, head and neck, and non-small-cell lung cancers with the recommended phase II rhizoxin dose of 2 mg m-2. Pharmacological studies were instituted with the phase II trials to complement the limited pharmacokinetic data available from the phase I trial. Blood samples were obtained from 69 of 103 eligible patients enrolled in phase II rhizoxin studies, and these were evaluable for pharmacokinetic analysis in 36 patients. Plasma rhizoxin concentrations were determined by high-performance liquid chromatography (HPLC), and post-distribution pharmacokinetic parameters were estimated by a one-compartment model. Rhizoxin was rapidly eliminated from plasma, with a median systemic clearance of 8.41 min-1 m-2 and an elimination half-life of 10.4 min. Rhizoxin area under the concentration-time curve (AUC) was higher in patients obtaining a partial response or stable disease than in those with progressive disease (median 314 vs 222 ng ml-1 min; P = 0.03). As predicted from previous studies, haematological and gastrointestinal toxicity was observed, but could not be shown to be related to rhizoxin AUC. This study demonstrated the rapid and variable elimination of rhizoxin from the systemic circulation. The presence of pharmacodynamic relationships and the low level of systemic toxicity suggest that future trials of rhizoxin with alternative dosage or treatment schedules are warranted.en
heal.journalNameBr J Canceren
heal.journalTypepeer-reviewed-
heal.fullTextAvailabilityTRUE-
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