Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
 
Paradigm shift in dosage determination of anticancer agents—Dosage based on MTD to tumor size
Hiroshi Maeda
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JOURNAL FREE ACCESS

2002 Volume 17 Issue 2 Pages 88-93

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Abstract
Traditional anticancer agents are mostly cytotoxic and small in molecular size. They distribute indiscriminately throughout the body, thus the high doge used in patients results in severe toxicity. Dose setting is based on maximum tolerable dose (MTD) ; and no way to escape the side effect at this dose. In contrast, polymeric drugs or microparticulates accumulate predominantly incancer tissue, if not 100%, which the mechanism is based on EPR-effect, Mechanism of EPR-effect is also described in the text. In any events, the dose should be based on the size of tumor ; large tumor needs large amount of drug. Such a good example is SMANCS/Lipiodol giver arterially for hepatoma ; this method can achieve a tumor/blood ratio of 2000, almost like missile. Accordingly, its good clinical result depends on dosing regimen based on tumor size. This concept will be appreciated as more such drugs with highly effective targeting become available.
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