Update: the potential for chemosensitization of alkylating agents by nitroimidazoles.
Extensive preclinical data suggest that nitroimidazole compounds, particularly misonidazole, can selectively potentiate the antitumor activity of certain bifunctional alkylating agents. Chemosensitization, as this phenomenon has been called, has now evolved to the critical stage of clinical evaluation. This report briefly reviews chemosensitization by nitroimidazoles and outlines theoretical concepts which in preclinical investigations have been shown to influence the expression of chemosensitization. These factors should be considered in the development of trials designed to assess the clinical efficacy of this treatment strategy. A re-examination of previous trials in light of these parameters suggests that many were not optimally designed to test the chemosensitization hypothesis. The hypothesis should be carefully evaluated in a limited number of trials incorporating, whenever possible, the lessons learned in the preclinical arena.
Mulcahy
R T
RT
University of Wisconsin, Clinical Cancer Center.
D000477:Alkylating Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D002986:Clinical Trials as Topic; D004249:DNA Damage; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009593:Nitroimidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D009593:Nitroimidazoles; D005978:Glutathione