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Multi-species toxicology approaches for oncology drugs

the US perspective
  • Joseph E. Tomaszewski
    Correspondence
    Tel.: +1-301-496-8777 (T&PB Office)/+1-301-435-9162 (Direct Line); fax: +1-301-480-4836
    Affiliations
    Chief, Toxicology & Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Executive Plaza North, Room 8034, 6130 Executive Boulevard, Rockville, MD 20852, USA
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      Abstract

      The Toxicology and Pharmacology Branch (T&PB) of the National Cancer Institute (NCI) performs pharmacological and toxicological evaluations of new oncology agents according to an agent-directed paradigm in which all studies are tailored to each agent. The United States Food and Drug Administration (US FDA) requires that preclinical toxicology studies be conducted in two species, a rodent and a non-rodent for all small molecules, and T&PB has successfully used this formula. While pharmacokinetic (PK) studies are considered optional, T&PB routinely develops new methods for plasma/tissue drug analysis and employs this methodology throughout development to determine kinetics in various species and toxicokinetics in the toxicity studies. In the current era of molecular target-based development, the T&PB also develops or employs methodology to evaluate effects of the new chemical entity on appropriate biomarkers in tumour and normal tissues. In this comprehensive programme, T&PB is able to correlate safety and toxicity with both plasma drug levels and biomarker modulation in two species for a seamless entry into Phase I.

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