Linked Life Data

11901539

Source:http://linkedlifedata.com/resource/pubmed/id/11901539

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-3-20
pubmed:abstractText
CI-980, (ethyl (S)-(5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b] pyrazine-7-yl) carbamate 2-hydroxyethansulfonate (1:1)), is a water-soluble mitotic inhibitor. It acts by binding to the colchicine-binding site on tubulin, a site different from that of the vinca alkaloids, inhibiting tubulin polymerization. Cells exposed to CI-980 accumulate in M phase and die. In preclinical tumor models, CI-980 showed a broad spectrum of activity, including in multi-drug resistant tumor cell lines, with activity at least equal to that of vincristine. Extensive small cell lung cancer, despite its responsiveness to chemotherapy, is usually an incurable disease with survival in patients of less than one year. Due to the preclinical activity of CI-980 and its similar mechanism of action to drugs effective in small cell lung cancer, a phase II trial in extensive small cell lung cancer was initiated by The Ohio State University Phase II Research Consortium. A "window of opportunity" design was chosen where a short six-week trial of the drug was given unless there was significant objective response. Twelve patients were entered in the study and underwent a total of 16 cycles of chemotherapy. The median age of the patients was 54 years old (range 34-71) and performance status was ECOG 0 (four patients), ECOG 1 (seven patients), and ECOG 2 (one patient). The patients were treated with a 72-hr infusion at a dose of 4.5 mg/m2/day. Toxicity was predominantly myelosuppression with granulocytopenia (nine episodes), and anemia (seven episodes). There were no objective responses with 11 patients being removed from study due to progressive disease. Evaluation of leukocyte microtubule structure in peripheral blood revealed microtubule depolymerization, which was seen after treatment (t = 72 hr) and was reversible within 24 hr of stopping the drug. We conclude that despite antitumor activity demonstrated in preclinical studies, CI-980 does not have biological activity in previously untreated small cell lung cancer at this dose and infusion protocol.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0735-7907
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
192-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
A phase II study of CI-980 in previously untreated extensive small cell lung cancer: an Ohio State University phase II research consortium study.
pubmed:affiliation
Division of Hematology/Oncology, James Cancer Hospital and Solove Research Institute, Ohio, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Multicenter Study, Clinical Trial, Phase II