Linked Life Data

9815562

Source:http://linkedlifedata.com/resource/pubmed/id/9815562

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-3-25
pubmed:abstractText
8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one (temozolomide) is a new imidazole tetrazinone compound with promising preclinical and clinical activity in nitrosourea-sensitive and -resistant models and manageable toxicity in Phase I and II clinical trials. In this study, we investigated the antiproliferative activity of temozolomide against a large variety of human tumors taken directly from patients in an in vitro soft agar tumor cloning system. Temozolomide was studied using a continuous exposure at final concentrations from 0.1 to 10.0 microM against a total of 222 tumor specimens, of which 101 (45%) were evaluable. A decrease in tumor colony formation was considered significant if survival of colonies treated with temozolomide was </=50% of that in controls. In vitro responses were seen in 9 of 101 [9%; 95% confidence interval (CI), 3-14], 16 of 100 (16%; 95% CI, 8. 5-23), and 35 of 101 (35%; 95% CI, 26-45) tumor specimens at concentrations of 0.1, 1.0, and 10.0 microM, respectively (P < 0. 001). The level of O6-guanine-alkyl-transferase was evaluable in 19 specimens before treatment but did not correlate with a response to temozolomide. At a concentration of 10 microM, a good cytotoxic activity was seen in breast (42%; 95% CI, 15-72), ovarian (36%; 95% CI, 11-69), and non-small cell lung cancers (27%; 95% CI, 6-61). Interestingly, activity was also seen in renal cell carcinomas (50%; 95% CI, 19-81), colon cancers (42%; 95% CI, 15-72), melanomas (33%; 95% CI, 13-59), and some other tumors, including sarcomas and both prostatic and pancreatic carcinomas that are usually considered very resistant to several conventional chemotherapy agents. Moreover, we observed that a subset of tumors that were not sensitive to dacarbazine, carmustine, cisplatin, doxorubicin, 5-fluorouracil, etoposide, and vinblastine were sensitive to temozolomide. These data indicate both that temozolomide is an active drug in vitro against a large variety of human tumors, including some tumors usually resistant to conventional chemotherapy, and that further clinical evaluation is warranted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1769-74
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9815562-Adrenal Gland Neoplasms, pubmed-meshheading:9815562-Antineoplastic Agents, pubmed-meshheading:9815562-Antineoplastic Agents, Alkylating, pubmed-meshheading:9815562-Brain Neoplasms, pubmed-meshheading:9815562-Breast Neoplasms, pubmed-meshheading:9815562-Cell Division, pubmed-meshheading:9815562-Dacarbazine, pubmed-meshheading:9815562-Digestive System Neoplasms, pubmed-meshheading:9815562-Dose-Response Relationship, Drug, pubmed-meshheading:9815562-Drug Resistance, Neoplasm, pubmed-meshheading:9815562-Female, pubmed-meshheading:9815562-Hematologic Neoplasms, pubmed-meshheading:9815562-Humans, pubmed-meshheading:9815562-Lung Neoplasms, pubmed-meshheading:9815562-Neoplasm Proteins, pubmed-meshheading:9815562-Neoplastic Stem Cells, pubmed-meshheading:9815562-O(6)-Methylguanine-DNA Methyltransferase, pubmed-meshheading:9815562-Tumor Cells, Cultured, pubmed-meshheading:9815562-Tumor Stem Cell Assay, pubmed-meshheading:9815562-Urogenital Neoplasms
pubmed:year
1997
pubmed:articleTitle
Activity of temozolomide against human tumor colony-forming units.
pubmed:affiliation
Translational Research Laboratory, Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, Texas 78245-3217, USA. dan_von_hoff@msmtp.iddw.saci.org
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't