Linked Life Data

11401916

Source:http://linkedlifedata.com/resource/pubmed/id/11401916

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-6-12
pubmed:abstractText
Individuals who receive life-saving organ transplants and the required immunosuppression often develop secondary cancers. One of the most common secondary cancers is nonmelanoma skin cancer in sun-exposed areas. Attempts to prevent these cancers have not been successful. Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), is a known experimental cancer prevention agent that is being evaluated in a number of human cancer prevention trials. This report describes a Phase I trial in 18 organ transplant recipients, randomized to 1.0 and 0.5 g of DFMO or a placebo, designed to look at short-term toxicities over 28 days as well as the impact of DFMO on two biological parameters, skin polyamines and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity. Blood levels of DFMO were also measured. The results indicate that DFMO was well tolerated over the 28-day period. The TPA-induced ODC activity in 3-mm skin biopsies was significantly lowered by 80 and 67% at the two dose levels. Polyamine levels were not affected significantly except for putrescine at the 0.5-g level. Blood levels of DFMO were about two times higher than expected, based on our prior pharmacokinetic studies. Our studies indicate that DFMO is a reasonable agent that should be tested further in larger Phase 2b trials in this population as a chemopreventive agent. TPA-induced ODC activity appears to be a relevant intermediate biological assay.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1055-9965
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
657-61
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Phase I chemoprevention study of difluoromethylornithine in subjects with organ transplants.
pubmed:affiliation
University of Wisconsin Comprehensive Cancer Center, Department of Medicine, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Clinical Trial, Phase I