Does Ro 03–8799 Concentration in Human Tumour Xenografts Predict Radiosensitization? Comparison with SR-2508

Abstract

Adams and Dewey¹ have proposed the use of electron-affinic compounds to overcome radioresistance of hypoxic cells in solid tumours. Although experimental results were promising, most of the clinical trials performed with metronidazole or misonidazole were unable to demonstrate a radiosensitizing effect of these drugs. These disappointing clinical results have been attributed largely to the fact that doses administered to patients were limited to low levels because of neurotoxicity. Etanidazole (SR-2508) and pjmonidazole (Ro 03–8799) which are less neurotoxic than misonidazole (MISO), are promising. Ro 03 8799 is particularly interesting, results obtained with rodent tumours, human tumour xenografts as well as with human tumours in patients indicate that this compound is more concentrated in the tumour than in the blood (Table 1). This tumour uptake is higher in melanomas than in other tumours and therefore a given amount of Ro 03–8799 should produce a higher radiosensitization in melanomas than in other tumours. This radiosensitization should also be higher than with SR-2508 (taking into account corrections for electron affinity differences) which is less concentrated in tumours than Ro 03–8799 (Table 1).