Criteria for selection of new analogs of antitumor antibiotics.
If a new analog of a known antitumor antibiotic is to justify interest, it must be demonstrated to possess either quantitative or qualitative superiority over the parent compound in pharmacologic, toxicologic, immunologic, tumor cytotoxic, or other biologic properties that are therapeutically favorable. The most commonly used criterion is in vivo activity in are therapeutically favorable. The most commonly used criterion is in vivo activity in experimental tumor systems. This may be demonstrated in primary screening systems or in secondary screening systems, or in refractory tumor systems, or in one or more tumors of a human xenograft panel. Data on adriamycin and bleomycin analogs give evidence of some of these approaches. An additional criterion for selection of analogs involves the demonstration of a broader spectrum of effectiveness against a panel of experimental systems. Actinomycin D is used as an exampled. There are a variety of factors that may be employed in determining further clinical interest for analogs of known antitumor antibiotics. It is important to delineate the limiting characteristics in the clinical application of the parent antitumor antibiotic and to the choose the appropriate systems to identify and characterize new analogs and investigate them in depth in order to determine whether they may provide some advantage either in antitumor selectivity or in the diminution of host toxicity with retention of antitumor effectiveness.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007700:Kinetics; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000628:therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009858:Oncogenic Viruses / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D004338:Drug Combinations