Linked Life Data

2306795

Source:http://linkedlifedata.com/resource/pubmed/id/2306795

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1990-4-4
pubmed:abstractText
Brequinar sodium (DUP 785, NSC 368390) is a novel quinoline-carboxylic acid derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its novel chemical structure. This compound inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHO-DH), which catalyzes the conversion of dihydroorotate to orotate, leading to a blockage in the pyrimidine de novo biosynthesis. A total of 43 patients received 110 courses of Brequinar sodium by short-term intravenous (i.v.) infusion, which was repeated every 3 weeks. Dose escalation was initially based on a modified Fibonacci scheme. After pharmacokinetic data from mice and man became available, a pharmacologically guided dose escalation was used; at toxic levels, dose escalation was applied on the basis of clinical judgement. The dose-limiting toxicities were myelosuppression, mucositis, skin rash, nausea and vomiting. The maximum tolerable doses for poor- and good-risk patients were 1,500 and 2,250 mg/m2, respectively. One mixed response was observed in a patient with papillary carcinoma of the thyroid. The recommended doses for phase II studies are 1,200 and 1,800 mg/m2 Brequinar sodium, given by a 1-h i.v. infusion every 3 weeks to poor- and good-risk patients, respectively.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
345-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Phase I study of Brequinar sodium (NSC 368390) in patients with solid malignancies.
pubmed:affiliation
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't