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THE RESISTANCE of hypoxic tumour cells to radiotherapy may be a common cause of local failure, for there is good evidence that hypoxic cells exist in nearly all human tumours which are treated. Among the methods which have been introduced to overcome this problem, the chemical radiosensitizers are the most recently developed (Adams et al., 1976). There is considerable interest in them for they have great potential for wide use in radiotherapy (Lancet, 1978). The first drug to be tested clinically for this purpose was metronidazole in 1973, shortly followed in 1974 by misonidazole (Ro 07-582, MISO) a much more effective drug in laboratory studies (Fowler et al., 1976). Now many clinical trials are under way with this compound in Europe, the In the early stages of testing MISO, as the dose was increased, the drug proved to be neurotoxic, producing encephalo-pathy and peripheral neuropathy (Dische et al., 1977). A dose limit of 12 g/m2 to be given over a period of not less than 17 days has now been generally accepted. With this dose limitation, most cases of peripheral neuropathy are mild and transient , but there is still an incidence of-30°%, and an occasional case of more severe toxicity (Dische et al., 1979). The dose may achieve a sensitization of hypoxic cells by a factor of 1-3-1-6 (Fowler et al., 1976) but this must be compared with a factor of 2-5-3 which is required to bring sensitization back to the level of that of oxic cells. Nevertheless there is an expectation that some of the current trials will show benefit with the use of the drug. A considerable effort is currently being made to develop new compounds which may lead to greater radiosensitization. A direct relationship has been demonstrated between the lipophilicity of radiosensi-tizing nitroimidazoles and neurotoxicity (Conroy, 1980). High tumour/brain concentration ratios have been obtained with drugs of relatively low lipophilicity (Brown & Lee, 1980). The alternative approach is to develop a compound with a shorter half-life in the plasma, for it has been shown in clinical as well as in animal studies that the area under the time curve of plasma concentration can be directly related to the incidence of neurotoxicity (Dische et al., 1979). The i.v. route has been considered as a potentially superior one, particularly with the use of some of the less lipophilic compounds (White et al., 1980); but this will reduce clinical …

A drug for improved radiosensitization in radiotherapy