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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-5-22
pubmed:abstractText
In vitro and clinical data suggest that cisplatin and carboplatin resistance may be overcome in some cases by dose escalation, although clinical toxicities limit this approach. Administration of platinum analogues in combination is an alternative dose-intensification strategy that has been little studied. The cytotoxicities of cisplatin (CDDP), carboplatin (CBDCA), and tetraplatin (TP, ormaplatin) alone and in combination were assayed by inhibition of the clonogenic survival of human ovarian-carcinoma cell lines (a) from an untreated patient (A2780), (b) selected for CDDP resistance in vitro (2780-CP70), and (c) from patients presenting with clinically refractory disease (OVCAR3, OVCAR10). The sensitivity patterns of these cell lines to platinum analogues were consistent with the existence of at least two platinum-resistance phenotypes - one being moderately resistant to CDDP and CBDCA but highly resistant to TP and the other being highly resistant to CDDP and CBDCA but only partially cross-resistant with TP. Effects of drug combinations were determined by median-effect analysis. Interactions between platinum analogues were variable in different cell lines. Synergistic cytotoxicity was apparent for the CDDP-CBDCA combination in the A2780 and OVCAR-3 cell lines and for the CDDP-TP combination in 2780-CP70 and OVCAR-3. Strong antagonistic effects were seen for CBDCA-TP in 2780-CP70. Platinum analogues showed additive effects in the remaining cell lines. These data suggest that there may be distinct sensitivity phenotypes for platinum-analogue combinations. The demonstration of in vitro synergy between platinum analogues supports their combined clinical use.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
430-4
pubmed:dateRevised
2006-4-24
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
In vitro interactions between platinum analogues in human ovarian-carcinoma cell lines.
pubmed:affiliation
Dept. of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
pubmed:publicationType
Journal Article