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See Latest ArticlesClinical potency of methotrexate, aminopterin, talotrexin and pemetrexed in childhood leukemias
Cancer Chemotherapy and Pharmacology, 10/05/09
Norris R et al. – Aminopterin does not appear to offer any advantage over methotrexate for the treatment of childhood ALL.
Methods- Compared in vitro cytotoxicity of methotrexate, aminopterin, pemetrexed, and talotrexin
- Panel of 6 pediatric leukemia and lymphoma cell lines using sulforhodamine B assay
- Also contrasted activity of drugs in context of clinically achievable (tolerable) drug exposures using area under plasma concentration–time curve (AUC)
- Defined each agent’s clinical potency index (CPI) as AUC achieved with standard pediatric dosing regimens divided by in vitro IC50
- Across all cell lines, talotrexin (median IC50 7 nM) and aminopterin (median IC50 17 nM) had lower IC50’s than methotrexate (median IC50 78 nM) and pemetrexed (median IC50 155 nM)
- CPI for methotrexate (median 0.9) significantly greater than that for aminopterin (median 0.4)
- CPI for methotrexate (median 0.9)significantly greater than that for aminopterin (median 0.4)
- Pemetrexed had significantly better CPI (median 13) than traditional antifols
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