Chemical sensitizers for hypoxic cells: a decade of experience in clinical radiotherapy.

The clinical work with chemical agents to restore the radiosensitivity of hypoxic cells began in 1973 with metronidazole, misonidazole was first given in 1974. The results so far recorded of the clinical trials with misonidazole have been generally disappointing. Only in 5 of 32 studies analyzed have significant benefits been shown to suggest real advantage with the use of misonidazole. Hypoxic cells must exist in all human tumours presenting for treatment and it is, however, probable that the oxygen effect is an important one at all dose fractionation regimes employed in radiotherapy but, after conventional fractionated radiotherapy, hypoxia may be a reason for failure in only a proportion of cases. The most important factor underlying the failure of misonidazole to achieve useful advantage is undoubtedly the low radiosensitizing concentrations achievable with the permitted dose of this neurotoxic drug. New drugs are under development and some have different dose-limiting toxicity. Those showing promise at this time are the Stanford compound, SR-2508, which is being extensively studied in the United States and the Roche compound, Ro 03-8799, which is being studied in the United Kingdom. It is possible that the greatest sensitization with the greatest tolerance will be achieved by a combination of drugs.