Clinical testing of the radiosensitizer Ro 07-0582: Experience with multiple doses

Abstract

The hypoxic cell radiosensitizer, Ro 07-0582 [1-(2-nitroimidazolyl)-3-methoxyisopropanal] was given in multiple doses to 16 patients. They received a total of 15-51 g im 3-20 doses. Immediate tolerance was good, and satisfactory plasma levels of the drug were consistently obtained. Neurotoxicity was troublesome: convulsions occurred in the patient given the highest dose, and there was peripheral neuropathy in 11 cases. Tumor concentrations similar to those in plasma were obtained in human tumors, in contrast to the findings in mouse tumors where concentrations are usually below 40% of plasma levels. In the treatment of human tumors, a lower dose of Ro 07-0582 should give useful hypoxic cell sensitization. Although the total dose of Ro 07-0582 must be limited, there is a real prospect that it will give benefit in clinical radiotherapy.