Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1993-11-2
pubmed:abstractText
Tirapazamine (SR 4233), a benzotriazine di-N-oxide, a potent and selective killer of hypoxic cells, is currently in Phase I clinical trials with the expectation that it will be combined with radiation therapy. However, because of the likelihood that hypoxic tumor cells may also be resistant to some commonly used chemotherapeutic agents, we have tested tirapazamine in combination with cisplatin (c-DDP) in the mouse RIF-1 tumor. A large, schedule-dependent enhancement of tumor cell killing was observed both in vivo and in vitro, with a maximal response observed when the SR 4233 was given 2-3 h before c-DDP. Assay of serum blood urea nitrogen levels following treatment with these two drugs indicates that SR 4233 does not enhance the kidney damage which can result from high doses of c-DDP. Leukopenia induced by the two drugs in combination was equal to that predicted from an additive effect of the responses to the individual drugs. Also, there was no change in the systemic toxicity of c-DDP (as judged by 50% lethal dose) when SR 4233 was combined with c-DDP at a dose and timing that produced the maximum tumor interaction. These observations point to a promising new combination therapy with considerable therapeutic advantage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4633-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin.
pubmed:affiliation
Department of Radiation Oncology, Stanford University School of Medicine, California 94305-5468.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't