Predicting the active doses in humans from animal studies: a novel approach in oncology

Eur J Cancer. 2007 Aug;43(12):1862-8. doi: 10.1016/j.ejca.2007.05.011. Epub 2007 Jul 2.

Abstract

The success rate of clinical drug development is significantly lower in oncology than in other therapeutic areas. Predicting the activity of new compounds in humans from preclinical data could substantially reduce the number of failures. A novel approach for predicting the expected active doses in humans from the first animal studies is presented here. The method relies upon a PK/PD model of tumour growth inhibition in xenografts, which provides parameters describing the potency of the tested compounds. Anticancer drugs, currently used in the clinic, were evaluated in xenograft models and their potency parameters were estimated. A good correlation was obtained between these parameters and the exposures sustained at the therapeutically relevant dosing regimens. Based on the corresponding regression equation and the potency parameters estimated in the first preclinical studies, the therapeutically active concentrations of new compounds can be estimated. An early knowledge of level of exposure or doses to be reached in humans will improve the risk evaluation and decision making processes in anticancer drug development.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy*
  • Random Allocation
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents