Linked Life Data

9180383

Source:http://linkedlifedata.com/resource/pubmed/id/9180383

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-9-2
pubmed:abstractText
The efficacy of the topoisomerase I inhibitor, 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptotheci n (irinotecan, CPT-11), administered by oral gavage has been examined against a panel of six independently derived neuroblastoma xenografts. Irinotecan was administered either daily for 5 days on 12 consecutive weeks ¿(d x 5)12¿ or for 5 days on two consecutive weeks repeated every 21 days for 4 cycles ¿[(d x 5)2]4¿. Given on the (d x 5)12 schedule the maximum tolerated dose (MTD) was 50 mg/kg. For intermittent scheduling ¿[(d x 5)2]4¿, the MTD was 75 mg/kg, resulting in the same total dose being administered (3 g/kg) over the period of treatment. At the MTD for the 12 consecutive week schedule there were two of 42 toxicity related deaths, whereas intermittent scheduling at the MTD resulted in none of 42 deaths. The intermittent schedule ¿[(d x 5)2]4¿ was less toxic than therapy given (d x 5)12, as at the end of treatment mice weighed 92 +/- 4% (SD; n = 6 experiments) and 81 +/- 4% (SD; n = 6 experiments) of their body weight at the start of therapy, respectively. The latter schedule was associated with loose feces starting around week 8 of therapy, broken teeth and a high incidence of swelling of the orbital conjunctiva that developed late in the course of therapy. Given (d x 5)12, irinotecan caused complete regressions of all six neuroblastoma xenograft lines. Because mice tolerate significantly greater systemic exposure to SN-38 lactone than do patients (as determined by plasma AUC at the respective MTD), we evaluated the intermittent schedule of administration, reducing the dose/administration to determine the lowest dose levels that produced objective regressions of these neuroblastoma xenografts and determined the daily systemic exposure associated with these dose levels. In four lines examined objective responses were obtained at dose levels of 12.5 or 6.25 mg/kg. The daily plasma AUC exposures associated with minimum dose achieving response in NB1691 (12.5 mg/kg), NB1643 (6.25 mg/kg) and NBEB (12.5 mg/kg) for irinotecan lactone were 219, 152 and 653 ng-h/ml, respectively; and for SN-38 lactone were 704, 418 and 987 ng-h/ml, respectively. These results indicate that childhood neuroblastoma xenografts are highly sensitive to irinotecan given by oral administration and therapeutic activity is similar to i.v. irinotecan administered on similar schedules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0959-4973
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
313-22
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Efficacy of oral irinotecan against neuroblastoma xenografts.
pubmed:affiliation
Department of Hematology Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't