Abstract
The goals of preclinical toxicology studies for oncology drugs are (1) to identify a starting dose that is both safe and that minimizes the number of patients treated with ineffective doses, (2) to identify important potential clinical toxicities, and (3) to assist in the design of human dosing regimens and escalation schemes (1). Toward these goals, studies are performed in animals to estimate the human maximally tolerated dose (MTD) and characterize drug-induced toxicities. Studies in both rodents and non-rodents to support Phase I trials have been expected by the U.S. Food and Drug Adminstration (FDA) since 1982 (2,3). In contrast, since 1981 clinical trials conducted under the auspices of the Cancer Research Campaign and the European Organization for the Research and Treatment of Cancer have relied on preclinical testing in rodents only for oncology drugs (4). The European Agency for the Evaluation of Medicinal Products has recently formalized this rodent-only approach as only acceptable for entry of cytotoxic oncology drugs with known mechansims of action into Phase I trials. For drugs with novel mechanisms of action, studies in rodents and non-rodents are currently expected (5).
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Clark, D.L., Andrews, P.A., Smith, D.D., DeGeorge, J.J., Justice, R.L., Beitz, J.G. (2000). Toxicology and Regulatory Aspects of Platinum Drugs. In: Kelland, L.R., Farrell, N.P. (eds) Platinum-Based Drugs in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-012-4_12
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DOI: https://doi.org/10.1007/978-1-59259-012-4_12
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