Role of preclinical pharmacology in phase I clinical trials: Considerations of schedule-dependence
Antitumor activity or host toxicity can be increased or decreased by changing the rate of drug delivery. This phenomenon is known as schedule-dependence, and the most familiar examples occur with the use of methotrexate (MTX), fluorodeoxyuridine (FdUrd), and cytosine arabinoside (ara-C). The general motivation for the study of schedule-dependence is to improve the therapeutic index of a drug, i.e., to maximize the ratio of therapeutic effects to toxic effects.
KeywordsContinuous Infusion Maximum Tolerable Dose Bolus Dose Antitumor Efficacy Cytosine Arabinoside
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- 2.Harrison SD, Dykes DJ, Plowman J, and Griswold DP: Evaluation of deoxyspergualin infusions against L1210 leukemia. Proc Amer Assoc Cancer Res. 27:277, 1986.Google Scholar
- 5.Lowe MC and Davis RD: Use of the mouse as a primary species for the preclinical toxicologic evaluation of oncolytic agents. Comparison of the results of a National Cancer Institute lethality/toxicity study of 20 drugs with historical data from clinical trials. Cancer Treat Rep, (to be published).Google Scholar