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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, Nicholasen
dc.contributor.authorHeinrich, B.en
dc.contributor.authorHuinink, W. W. Ten Bokkelen
dc.contributor.authorWagener, D. J. Then
dc.contributor.authorAamdal, S.en
dc.contributor.authorVerweij, J.en
dc.creatorMcLeod, H. L.en
dc.creatorMurray, L. S.en
dc.creatorWanders, J.en
dc.creatorSetanoians, A.en
dc.creatorGraham, M. A.en
dc.creatorPavlidis, Nicholasen
dc.creatorHeinrich, B.en
dc.creatorHuinink, W. W. Ten Bokkelen
dc.creatorWagener, D. J. Then
dc.creatorAamdal, S.en
dc.creatorVerweij, J.en
dc.date.accessioned2018-06-22T09:54:01Z
dc.date.available2018-06-22T09:54:01Z
dc.date.issued1996
dc.identifier.urihttps://gnosis.library.ucy.ac.cy/handle/7/42154
dc.description.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 T 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
dc.language.isoengen
dc.sourceBritish journal of canceren
dc.subjectArticleen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectHumanen
dc.subjectHumansen
dc.subjectBreast canceren
dc.subjectBreast neoplasmsen
dc.subjectMajor clinical studyen
dc.subjectPriority journalen
dc.subjectAlopeciaen
dc.subjectClinical trialen
dc.subjectDiarrheaen
dc.subjectLeukopeniaen
dc.subjectMucosa inflammationen
dc.subjectMulticenter studyen
dc.subjectPhase 2 clinical trialen
dc.subjectStomatitisen
dc.subjectTreatment outcomeen
dc.subjectIntravenousen
dc.subjectArea under the curveen
dc.subjectPainen
dc.subjectLung neoplasmsen
dc.subjectLung non small cell canceren
dc.subjectMelanomaen
dc.subjectCarcinomaen
dc.subjectInjectionsen
dc.subjectGastrointestinal symptomen
dc.subjectIntravenous drug administrationen
dc.subjectBlood toxicityen
dc.subjectDrug clearanceen
dc.subjectPharmacokineticsen
dc.subjectAntineoplasticen
dc.subjectDrug blood levelen
dc.subjectDrug half lifeen
dc.subjectArea under curveen
dc.subjectHigh performance liquid chromatographyen
dc.subjectSkin toxicityen
dc.subjectAstheniaen
dc.subjectNon-small-cell lungen
dc.subjectHead and neck canceren
dc.subjectHead and neck neoplasmsen
dc.subjectAntibioticsen
dc.subjectLactonesen
dc.subjectMacrolidesen
dc.subjectPhase ii trialen
dc.subjectRhizoxinen
dc.subjectDrug determinationen
dc.subjectDrug eliminationen
dc.subjectPharmacodynamicsen
dc.titleMulticentre phase II pharmacological evaluation of rhizoxinen
dc.typeinfo:eu-repo/semantics/article
dc.description.volume74
dc.description.issue12
dc.description.startingpage1944
dc.description.endingpage1948
dc.author.facultyΙατρική Σχολή / Medical School
dc.author.departmentΙατρική Σχολή / Medical School
dc.type.uhtypeArticleen
dc.contributor.orcidPavlidis, Nicholas [0000-0002-2195-9961]
dc.gnosis.orcid0000-0002-2195-9961


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