ABSTRACT
A difficult area for decision making involves the selection of new analogs of conventional cytostatic agents for clinical trials. A number of preclinical criteria may be used to develop these analogs for quantitative or qualitative superiority over the parent coumpound in properties based on pharmacology, therapy, or toxicology. Cytidine analogs have been developed to generate compounds with a broader spectrum of activity, that is, against solid tumor types. The nude mouse-human tumor model is gaining interest for its application in the secondary screening of promising analogs of conventional cytostatic agents. Cyclophosphamide and ifosfamide belong to the group of oxazaphosphorine cytostatic agents which have been synthesized to convert the reactive nitrogen mustard group in an inactive transport form. The cytidine antimetabolites, ara-C (arabinosyl-5-azacytosine) and 5-azacytidine, are effective anti tumor agents in the treatment of acute leukemias. Several critical remarks have to be added to enlighten some of the difficulties encountered with analogs rather than with unrelated investigational agents.
