Experimental Models and their Predictive Value in New Drug Development: A Critical Appraisal: I. Toxicity Models.
The toxicity of antitumor agents for the host constitutes a prime limiting factor in clinical chemotherapy and it is essential that models be employed which will predict for both the quantitative and qualitative toxicity of new drugs undergoing development (1–4). The potential risks for the patient are significant: a) in order to maximize therapeutic efficacy and with the goal of cure, doses of drug in a moderately toxic range are generally employed; b) the testing of new compounds in the clinic is frequently accomplished with patients who have received prior therapy or are in an advanced stage of disease, so that the ability to withstand drug toxicity is diminished; c) the patients are usually treated for an extended period of time with repeated regimens. Further, many of the antitumor agents act via cytotoxicity for the host, increasing the risk of mutagenesis, carcinogenesis and teratogenesis.
KeywordsToxicity Pancreatitis Anemia Doxorubicin Methotrexate
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