Application of preclinical data to initiate the modified continual reassessment method for maximum tolerated dose-finding trials.
This study was conducted to evaluate whether the allometric approach can be used to predict maximum tolerated dose (MTD) in humans from animal data. Twenty-five anticancer drugs were taken from the literature and used in this analysis. The results of the study indicate that MTD can be predicted with reasonable accuracy using interspecies scaling. The predicted MTD can then be applied to the modified continual reassessment method retrospectively for the selection of initial and subsequent doses of anticancer drugs in the patient population. This approach can save time and avoid many unnecessary steps to attain MTD in humans if it could be applied prospectively.
Mahmood
I
I
Division of Pharmaceutical Evaluation I, Office of Clinical Pharmacology and Biopharmaceutics (HFD-860), Food and Drug Administration (FDA), Rockville, Maryland, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D000882:Haplorhini; D006801:Humans; D020714:Maximum Tolerated Dose; D051379:Mice; D008954:Models, Biological; D011237:Predictive Value of Tests; D051381:Rats; D013045:Species Specificity
D000970:Antineoplastic Agents