Preclinical anti-tumor activity of a new oral platinum(IV) drug LA-12
Language English Country Great Britain, England Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15930894
DOI
10.1097/00001813-200507000-00010
PII: 00001813-200507000-00010
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma drug therapy MeSH
- Amantadine administration & dosage analogs & derivatives MeSH
- Administration, Oral MeSH
- Mice, Inbred Strains MeSH
- Humans MeSH
- Maximum Tolerated Dose MeSH
- Disease Models, Animal MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Ovarian Neoplasms drug therapy MeSH
- Organoplatinum Compounds administration & dosage MeSH
- Plasmacytoma drug therapy MeSH
- Antineoplastic Agents administration & dosage MeSH
- Drug Screening Assays, Antitumor methods MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Amantadine MeSH
- bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) MeSH Browser
- Organoplatinum Compounds MeSH
- Antineoplastic Agents MeSH
- satraplatin MeSH Browser
A novel anti-tumor platinum(IV) complex, coded as LA-12, with a bulky adamantylamine ligand displaying oral activity was prepared and its oral activity was evaluated. The murine ADJ/PC6 plasmacytoma and human A2780 ovarian carcinoma tumor model were used to evaluate the in vivo anti-tumor activity of a single dose and also of repeated doses with comparison to the activity of cisplatin and of the platinum(IV) complex satraplatin. The acute toxicity of LA-12 in mice is relatively low (maximum tolerated dose 1000 mg/kg), and the effective dose is comparable to that of cisplatin and higher than that of satraplatin. The therapeutic index derived from this is very high (250). In the human tumor model, two repeated dose schedule regimens were evaluated. LA-12 exerted a significantly higher anti-tumor activity than other substances, i.e. cisplatin and satraplatin, in repeated doses on the murine ADJ/PC6 plasmacytoma tumor model. The dailyx5 repeated dose regimen was selected for further evaluation.
References provided by Crossref.org
The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo
