Tumour
hypoxia is a negative factor in
cancer radiotherapy. In order to overcome the problem, various
pharmacotherapies have been investigated as an adjunct to
radiotherapy. The use of hypoxic cell sensitisers is a classical strategy, and many new compounds have been developed and investigated. Development of more efficient compounds than those currently available seems difficult and clinical studies to prove the efficacy of the existing compounds are encouraged, especially in combination with radiosurgery, intraoperative
radiotherapy, and interstitial irradiation, in which a single high dose of radiation is used. Following the advent of hypoxic cell sensitisers, hypoxic
cytotoxins have become available. Among them,
tirapazamine has already gained success when combined with
cisplatin in
non-small cell lung cancer. The beneficial effect of
tirapazamine when combined with radiation needs to be determined. As a third-generation compound in this field, antitumour
prodrugs that are activated by irradiation under hypoxic conditions via one-electron reduction have been proposed.
Prodrugs of
5-fluorouracil and
5-fluoro-2'-deoxyuridine have shown in vivo as well as in vitro activity. Although clinical evaluation of the compounds is not warranted due to a relatively low in vivo effect, this strategy appears promising if the
prodrug design can be applied to more potent agents that shall be developed in future.