Linked Life Data

7634381

Source:http://linkedlifedata.com/resource/pubmed/id/7634381

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-9-13
pubmed:abstractText
The efficacy of protracted schedules of therapy of the topoisomerase I inhibitors 9-dimethyl-aminomethyl-10-hydroxycamptothecin (topotecan) and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (irinotecan; CPT-11) were evaluated against a panel of 21 human tumor xenografts derived from adult and pediatric malignancies. Tumors included eight colon adenocarcinomas, representing an intrinsically chemorefractory malignancy, six lines derived from childhood rhabdomyosarcoma (three embryonal, three alveolar) representing a chemoresponsive histiotype, sublines of rhabdomyosarcomas selected in vivo for resistance to vincristine and melphalan, and three pediatric brain tumors. All tumors were grown at the subcutaneous site. Topotecan was administered by oral gavage 5 days per week for 12 consecutive weeks. The maximum tolerated dose (MTD) was 1.5 mg/kg per dose. Irinotecan was given by i.v. administration daily for 5 days each week for 2 weeks [(d x 5)2](one cycle of therapy), repeated every 21 days. The MTD for three cycles was 10 mg/kg per dose. Treatment was started against advanced tumors. Topotecan caused a high frequency of objective regressions in one of eight colon tumor lines, whereas irinotecan caused complete regressions (CR) of all tumors in three colon lines and a high frequency of CRs in three additional lines. Both drugs demonstrated similar activity against rhabdomyosarcoma xenografts. Topotecan caused CR of all tumors in four of six lines, and irinotecan in five of six lines evaluated. Both agents retained full activity against tumors selected for primary resistance to vincristine, but only irinotecan retained activity against a tumor selected for primary resistance to melphalan. Both agents demonstrated good activity against brain tumor xenografts with irinotecan causing CR in two of three lines and topotecan inducing CR in one of three lines. Results indicate that low-dose protracted schedules of daily administration of these topoisomerase I inhibitors is either equi-effective or more efficacious than more intense shorter schedules of administration reported previously.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
393-403
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:7634381-Adenocarcinoma, pubmed-meshheading:7634381-Animals, pubmed-meshheading:7634381-Antineoplastic Agents, pubmed-meshheading:7634381-Antineoplastic Agents, Phytogenic, pubmed-meshheading:7634381-Brain Neoplasms, pubmed-meshheading:7634381-Camptothecin, pubmed-meshheading:7634381-Colonic Neoplasms, pubmed-meshheading:7634381-Female, pubmed-meshheading:7634381-Humans, pubmed-meshheading:7634381-Mice, pubmed-meshheading:7634381-Mice, Inbred CBA, pubmed-meshheading:7634381-Neoplasms, Experimental, pubmed-meshheading:7634381-Random Allocation, pubmed-meshheading:7634381-Rhabdomyosarcoma, pubmed-meshheading:7634381-Topoisomerase I Inhibitors, pubmed-meshheading:7634381-Topotecan, pubmed-meshheading:7634381-Transplantation, Heterologous, pubmed-meshheading:7634381-Tumor Cells, Cultured
pubmed:year
1995
pubmed:articleTitle
Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors.
pubmed:affiliation
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38101, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't