The use of halogenated thymidine analogs as clinical radiosensitizers: rationale, current status, and future prospects: non-hypoxic cell sensitizers.
The halogenated pyrimidine analogs, bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR) have been recognized as potential clinical radiosensitizers for over two decades. In vivo and in vitro experimental studies document that radiosensitization is directly dependent on the amount of thymidine replacement in DNA by these analogs. Early clinical studies in Japan using selective intra-arterial infusions of BUdR and conventional fractionated radiation suggested improved survival in patients with primary brain tumors, although there were significant catheter-related complications. Based on recent in vivo and clinical pharmacology studies on continuous intravenous infusions of these drugs, clinical trials are underway evaluating the potential of radiosensitization in high grade gliomas and other poorly radioresponsive tumors using the technically safer intravenous route of administration. In this paper, we review the basic strategy for the use of these analogs, the ongoing clinical trials and the potential areas for future experimental and clinical studies.
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D001973:Bromodeoxyuridine / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D006224:Cricetinae; D004260:DNA Repair; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D007065:Idoxuridine / Q000627:therapeutic use*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine; D007065:Idoxuridine