[Clinical trials of hypoxic cell sensitizer misonidazole]

Misonidazole is the first hypoxic cell sensitizer which is introduced into the world-wide clinical trials. More than 500 patients have been treated with misonidazole in Japan. Phase I study, involved 106 patients, established its pharmacology, toxicities and safe dose regimens to Japanese. Total amount of 10.0g/m2, 1.5g/m2 once, 1.0g/m2 twice and 0.5g/m2 5 times a week, can be administered with acceptable toxicities and give plasma levels of the sensitizer enough to expect sensitizing effect to a certain degree. Several preliminary studies demonstrated the effect of the drug by factor about 1.3 in tumor regression, however the results of most Phase II studies were controversial. Final determination of its efficacy should be postponed until the completion of randomized Phase III studies with large number of patients, which are ongoing in the United States, Japan and so on. Considering the neurotoxicity of misonidazole, it is not the ideal sensitizer, but should be regarded as the first generation drug for hypoxic cells. Since a number of less toxic sensitizers are under development at present, more effective and safe drugs will appear in the near future.