Linked Life Data

8980394

Source:http://linkedlifedata.com/resource/pubmed/id/8980394

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-1-27
pubmed:abstractText
Rhizoxin 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.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-1450065, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-1545439, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-1581905, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-2364385, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-2898289, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-3753552, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-7720174, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-7799018, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-7901342, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-7907130, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-8562349, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-8562350, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-8562351, http://linkedlifedata.com/resource/pubmed/commentcorrection/8980394-8911111
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0007-0920
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1944-8
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Multicentre phase II pharmacological evaluation of rhizoxin. Eortc early clinical studies (ECSG)/pharmacology and molecular mechanisms (PAMM) groups.
pubmed:affiliation
Department of Medical Oncology, University of Glasgow, UK.
pubmed:publicationType
Journal Article, Clinical Trial, Multicenter Study, Clinical Trial, Phase II