Predictive model for plasma concentration-versus-time profiles of investigational anticancer drugs in patientsi

Lisa E. Davis, David S. Alberts, Patricia M. Plezia, Denise J. Roe, Daniel P. Griswold

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We report a model that provides a strong correlation between mouse toxicity data [mouse lethal dose 10% (LD10)] and human plasma concentration-versus-time (CXT) data for 22 commonly used anticancer agents. Mouse toxicity data (LD10) from two dosing schedules, daily times one and daily times seven, were evaluated for the two mouse strains BDF/1 and Swiss. Data from BDF/1 mice were selected for analysis because they were more abundant. Strong correlations were found between LD10 and human plasma CXT data for both daily times one and daily times seven dosing schedules-In (CXT) = -1.6504 + [0.8408 × In (LD10)], r = .84, P < .0001, and In (CXT) = -0.0754 + [0.8954 × In (LD10)], r = .90, P < .0001, respectively. These correlations may serve as useful models to predict the maximally tolerated dose of an investigational anticancer agent prior to entry into clinical trials and to assist in the selection of clinically relevant in vitro CXTs for new-agent screening against human tumors.

Original languageEnglish (US)
Pages (from-to)815-819
Number of pages5
JournalJournal of the National Cancer Institute
Volume80
Issue number11
DOIs
StatePublished - Aug 3 1988

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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