Clinical trials with hypoxic cell sensitizers: time to retrench or time to push forward?
Results of world-wide clinical trials with misonidazole are discussed. An attempt is made to assess the reasons for the lack of positive results and the cost-benefit analysis is critically reviewed. The data on the clinical investigations of the second generation misonidazole analogues SR-2508 and RO-03-8799 are presented. Emphasis is placed on future work such as tumor selection for clinical trials, reduction of drug toxicity and methods to increase the drug radiosensitizing properties. Because of the large amount of knowledge, experience, productivity and good scientific clinical data accummulated with nitroimidazoles over the past five years, it is recommended that this is the time to push forward with the work on the newest, more efficient compounds.
D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use; D004341:Drug Evaluation; D017341:Etanidazole; D006801:Humans; D008920:Misonidazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D009593:Nitroimidazoles / Q000627:therapeutic use*; D010100:Oxygen / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D017341:Etanidazole; C033815:pimonidazole; D003907:Dexamethasone; D008920:Misonidazole; C009997:desmethylmisonidazole; D010100:Oxygen