Promise of radiosensitizers and radioprotectors in the treatment of human cancer
Over the past 30 years, as an understanding of radiation chemistry has developed, it has been possible to develop compounds which modify the initial radiochemical event. In addition, certain physiologic means such as hyperbaric oxygen or blood flow restriction have also been developed as methods to modify radiation response through the radiochemical processes. Following the success of certain hyperbaric trials, a great effort was made to develop chemical agents which would mimic oxygen in their sensitization of hypoxic cells. A large series of compounds have now been identified with such properties and several of these have entered clinical trial. The first compound to receive widespread testing, misonidazole, has proven too toxic to be used in adequate doses for clinically relevant sensitization. Two new nitroimidazole analogs, which are excluded from the central nervous system, promise to allow much higher degrees of sensitization in planned clinical trials and new non-nitro drugs are under development. Radioprotection can be achieved through various methods, including restriction in blood flow and the use of sulfhydryl-containing compounds which again modify the initial radiochemical events. To be successful in tumor therapy, such agents must be selective in protecting the normal tissues. One class of compounds, the thiophosphates, show differential protection of normal tissue vis-a-vis tumor through several mechanisms. After extensive animal testing, one of these compounds, WR 2721, is now in phase I clinical testing, with phase II evaluation planned for the near future. Other potential sensitizers with varying degrees of differential activity in tumor versus normal tissue are also discussed.
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 6354445
- Journal Information:
- Cancer Treat. Rep.; (United States), Vol. 68:1
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
RADIOSENSITIZERS
TESTING
CARCINOMAS
IMIDAZOLES
MISONIDAZOLE
RADIATION PROTECTION
RADIOPROTECTIVE SUBSTANCES
RADIOTHERAPY
THIOLS
TOXICITY
ANTINEOPLASTIC DRUGS
AZOLES
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
MEDICINE
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOLOGY
THERAPY
560151* - Radiation Effects on Animals- Man
550603 - Medicine- External Radiation in Therapy- (1980-)