Abstract | PURPOSE: Renewed interest in antifols for the treatment of childhood cancers has resulted from identification of novel antifols with broad spectrums of anti- cancer activity and from re-evaluation of the original clinical antifol, aminopterin. In this pre-clinical study we evaluated the in vitro activity of both traditional antifols ( methotrexate, aminopterin) and novel antifols ( pemetrexed, talotrexin) in childhood acute leukemias and lymphomas. METHODS: We compared the in vitro cytotoxicity of methotrexate, aminopterin, pemetrexed, and talotrexin in a panel of six pediatric leukemia and lymphoma cell lines using the sulforhodamine B assay. In addition to defining a 50% growth inhibitory concentration (IC50) for a 120-h drug exposure, we contrasted the activity of the drugs in the context of clinically achievable (tolerable) drug exposures using the area under the plasma concentration-time curve (AUC). We defined each agent's clinical potency index ( CPI) as the AUC achieved with standard pediatric dosing regimens divided by the in vitro IC50. RESULTS: CONCLUSIONS:
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Authors | Robin E Norris, Peter C Adamson |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 65
Issue 6
Pg. 1125-30
(May 2010)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 19784838
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antineoplastic Agents
- Folic Acid Antagonists
- Glutamates
- Pterins
- Pemetrexed
- N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine
- Guanine
- Ornithine
- Aminopterin
- Methotrexate
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Topics |
- Aminopterin
(chemistry, pharmacology)
- Antineoplastic Agents
(chemistry, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Child
- Dose-Response Relationship, Drug
- Folic Acid Antagonists
(chemistry, pharmacology)
- Glutamates
(chemistry, pharmacology)
- Guanine
(analogs & derivatives, chemistry, pharmacology)
- Humans
- Inhibitory Concentration 50
- Jurkat Cells
- Leukemia
(pathology)
- Lymphoma
(pathology)
- Methotrexate
(chemistry, pharmacology)
- Molecular Structure
- Ornithine
(analogs & derivatives, chemistry, pharmacology)
- Pemetrexed
- Pterins
(chemistry, pharmacology)
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