[Present status of radiation sensitizers--hypoxic cell radiosensitizer]

There is a world-wide demand for a clinically usable sensitizer for radio resistant hypoxic cells. Since the unsuccessful clinical trials of misonidazole (MISO), is due to its neurotoxicity, many efforts have been made to develop new hypoxic cell sensitizers which is more effective and/or less toxic than MISO. In the U.S.A., SR-2508 (etanidazole) is currently under going phase III clinical evaluation in advanced head and neck cancers, and in England, Ro 03-8799 (pimonidazole) is also under going phase III evaluation in advanced cervical cancer. Also in Japan, many compounds were synthesized and tested with the screening systems using EMT6 and SCCVII tumors. KU-2285 is fluorinated nitroimidazole and it has a higher sensitizing effect than MISO or etanidazole. Its sensitizing effect is 1.65 at 200 mg/kg, and the LD50 value is 2.3 g/kg. Hoping for less neurotoxicity, RK-28, RP-170 and KIH-802 were synthesized. RP-170 showed the same advantages over MISO as etanidazole in terms of sensitization or toxicity and KIH-802 demonstrated an unexpectedly high sensitizing effect especially in vivo experiments. Although RK-28 has a low LD50 value, it shows rapid clearance rate from serum and is supposed to have less cumulative neurotoxicity. RK-28 has already entered to phase I clinical trial and KU-2285, RP-170 and KIH-802 are also waiting further clinical trials.