Dependence of misonidazole radiosensitization on drug and radiation schedules

Animal trials with misonidazole (MISO) have shown that maximum tumor sensitization requires radiation schedules different from those in clinical use. These radiation schedules provide suboptimal radiotherapy. The authors are using a rat model to determine whether MISO can sensitize in multi-fraction studies at the drug levels that can be tolerated in humans. Using a nonimmunogenic tumor in unanesthetized rats, they have measured MISO sensitization for single treatments (25-600 mg/kg), and for multifraction regimens in which MISO was given each radiation fraction (25-600 mg/kg/fraction). They found that for equal MISO dose per fraction sensitization decreases as the radiation dose per fraction decreases. From sensitization measured for low MISO and radiation doses per fraction the authors project that clinically significant sensitization will require schedules which allow MISO to be used at doses of 1.5 g/m/sup 2/ with every dose of radiation. With the total MISO dose limited to 12 g/m/sup 2/, this requires a nonstandard radiation schedule, or a sensitizer considerably more potent than MISO