Linked Life Data

12522437

Source:http://linkedlifedata.com/resource/pubmed/id/12522437

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-1-10
pubmed:abstractText
A large number of adenoviral agents are being developed for the treatment of cancer. However, the treatment-related death of a patient with ornithine transcarbamylase deficiency following adenovirus administration by hepatic artery has led to serious concerns regarding the safety of intravascular adenovirus. Both replication-incompetent (rAd.p53, e.g., SCH58500) and replication-selective (dl1520, aka Onyx-015; CG7870) oncolytic adenoviruses, by intravascular administration, are in clinical trials. We review Phases I and I/II results from these clinical trials. dl1520 and rAd.p53 were well-tolerated following hepatic artery infusion at doses of up to 2x10(12) and 2.5x10(13) particles, respectively. At a dose of 7.5x10(13) particles, rAd.p53 was associated with dose-limiting cardiac output suppression; dl1520 dose escalation did not proceed higher than 2x10(12). Intravenous (i.v.) infusions of dl1520 and CG7870 have been well tolerated by i.v. infusion at doses of 2x10(13) and 6x10(12), respectively, without identification of a maximally tolerated dose to date. Mild/moderate transaminitis was demonstrated in some patients on both the hepatic arterial and i.v. trials at doses >or=10(12) particles. Interleukin (IL)-6 and IL-10 were induced in a dose-dependent manner in most patients, but significant interpatient and intrapatient (on repeat doses) variabilities were demonstrated. Evidence of p53 gene expression (Ad.p53) or viral replication (dl1520) was demonstrated in the majority of patients receiving >or=10(12) particles. Over 100 cancer patients have been treated with intravascular adenovirus constructs to date with an acceptable toxicity profile; further clinical trial testing appears appropriate in cancer patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
979-86
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Intravascular adenoviral agents in cancer patients: lessons from clinical trials.
pubmed:affiliation
Stanford University, Palo Alto Veterans Administration Hospital, Palo Alto, California, USA.
pubmed:publicationType
Journal Article, Review