Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
1994-9-29
|
| pubmed:abstractText |
The camptothecin derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy camptothecin (CPT-11) has attracted the attention of clinicians because of its high antitumor activity against refractory solid cancers. We established two CPT-11-resistant cell lines, a non-small-cell lung-cancer cell line (PC-7/CPT-11) from the parental PC-7 line and an ovarian cancer cell line (HAC-2/CPT-11) from the parental HAC-2 line. The mechanisms of resistance to CPT-11 in PC-7/CPT-11 cells were reduced conversion of CPT-11 to its active metabolite SN-38 and point mutation topoisomerase I. Those in HAC-2/CPT-11 cells were reduction of topoisomerase I activity and decreased sensitivity of topoisomerase to topoisomerase I inhibitors. No point mutation of the topoisomerase was observed in HAC-2/CPT-11 cells. We conducted two phase I trials using CPT-11 in combination with other anticancer agents. One was a phase I trial of CPT-11 and cisplatin given with a fixed dose of vindesine to patients with advanced non-small-cell lung-cancer and the other was a phase I study on a topoisomerase-targeting combination of CPT-11 and etoposide (VP-16) in patients with various malignant solid tumors. The results of the first trial indicated that the recommended dose of CPT-11 for phase II studies was 80 mg/m2 combined with 3 mg/m2 vindesine on days 1 and 8 and 60 mg/m2 cisplatin on day 1. In the second trial, the recommended dose of CPT-11/VP-16 given with recombinant granulocyte colony-stimulating factor (on days 4-17) was found to be 60/60 mg/m2. In both trials, diarrhea and granulocytopenia were considered to be dose-limiting toxicities.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/irinotecan
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0344-5704
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
34 Suppl
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
S112-7
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:8070019-Amino Acid Sequence,
pubmed-meshheading:8070019-Animals,
pubmed-meshheading:8070019-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:8070019-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:8070019-Base Sequence,
pubmed-meshheading:8070019-CHO Cells,
pubmed-meshheading:8070019-Camptothecin,
pubmed-meshheading:8070019-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:8070019-Cell Line,
pubmed-meshheading:8070019-Cell Survival,
pubmed-meshheading:8070019-Clinical Trials, Phase I as Topic,
pubmed-meshheading:8070019-Cricetinae,
pubmed-meshheading:8070019-DNA Topoisomerases, Type I,
pubmed-meshheading:8070019-Drug Resistance,
pubmed-meshheading:8070019-Etoposide,
pubmed-meshheading:8070019-Female,
pubmed-meshheading:8070019-Humans,
pubmed-meshheading:8070019-Lung Neoplasms,
pubmed-meshheading:8070019-Molecular Sequence Data,
pubmed-meshheading:8070019-Neoplasms,
pubmed-meshheading:8070019-Ovarian Neoplasms,
pubmed-meshheading:8070019-Point Mutation,
pubmed-meshheading:8070019-Topoisomerase I Inhibitors,
pubmed-meshheading:8070019-Tumor Cells, Cultured
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
7-Ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin: mechanism of resistance and clinical trials.
|
| pubmed:affiliation |
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
|
| pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
|