title: Multi-species toxicology approaches for oncology drugs: the US perspective.
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.
authors.affiliation: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Executive Plaza North, Room 8034, 6130 Executive Boulevard, Rockville, MD 20852, USA. tomaszej@mail.nih.gov
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tomaszewski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001709:Biotechnology; D015195:Drug Design; D004341:Drug Evaluation / Q000379:methods; D005544:Forecasting; D020714:Maximum Tolerated Dose; D023421:Models, Animal; D009369:Neoplasms / Q000188:drug therapy*; D014481:United States
chemical_list: D000970:Antineoplastic Agents