Clinical experience with misonidazole: high dose fractions versus daily low doses

In April 1976 clinical experience with misonidazole began at the University Clinic for Radiotherapy and Radiobiology of Vienna. Initially the drug was given mainly in four to six divided large doses ranging from 50 to 80 mg/kg (2.1-3.1 g/m2). Since October 1977 daily low doses in the range of 1-2g (0.45-1.3 g/m2) were used. So far over 100 patients with advanced tumor stages have been under investigation. Serum levels for the different treatment schedules are reviewed and sensitizer enhancement ratios larger than 1.3 may be expected even with daily low doses of misonidazole. Neurological side effects are analyzed and related to the cumulative dose (in g/m2) and overall treatment time. Depending on the overall time of drug administration the total dose of misonidazole can be adjusted to avoid undersirable side effects. It is our impression that normal tissue reactions are unchanged by the use of misonidazole. Preliminary results of a randomized clinical trial in patients with high-grade astrocytomas appear to be favorable for the sensitizer group. Als some impressive clinical results were seen in patients when using daily low doses of misonidazole.