PROMISE OF RADIOSENSITIZERS AND RADIOPROTECTORS IN THE TREATMENT OF HUMAN CANCER

Abstract

Over the past 30 yr, 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 O2 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 O2 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 1st compound to receive widespread testing, misonidazole, proved too toxic to be used in adequate doses for clinically relevant sensitization. Two new nitroimidazole analogs, which are excluded from the CNS, promise to allow much higher degrees of sensitization in planned clinical trials; new non-nitro drugs are under development. Radioprotection can be achieved through various methods, including restriction in blood flow and the use of SH-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 [S-2-(3-aminopropylamino)ethylphosphorothioic acid], is now in phase I clinical testing, with phase II evaluation planned for the near future. Other potential sensitizers with varyig degrees of differential activity in tumor vs. normal tissue are also discussed.