Role of preclinical pharmacology in phase I clinical trials: Considerations of schedule-dependence

  • Jerry M. Collins
  • Brian Leyland-Jones
  • Charles K. Grieshaber
Part of the Cancer Treatment and Research book series (CTAR, volume 36)


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.


Continuous Infusion Maximum Tolerable Dose Bolus Dose Antitumor Efficacy Cytosine Arabinoside 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Driscoll JS: The preclinical new drug research program of the National Cancer Institute. Cancer Treat Rep 68:63–76, 1984.PubMedGoogle Scholar
  2. 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
  3. 3.
    Sikic BI, Collins JM, Mimnaugh EG, and Gram TE: Improved therapeutic index of bleomycin when administered by continuous infusion in mice. Cancer Treat Rep 62:2011–2017, 1978.PubMedGoogle Scholar
  4. 4.
    Collins JM, Zaharko DS, Dedrick RL, and Chabner BA: Potential roles for preclinical pharmacology in phase I trials. Cancer Treat Rep 70:73–80, 1986.PubMedGoogle Scholar
  5. 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

Copyright information

© Martinus Nijhoff Publishers, Boston 1987

Authors and Affiliations

  • Jerry M. Collins
  • Brian Leyland-Jones
  • Charles K. Grieshaber

There are no affiliations available

Personalised recommendations