Combined treatment of radiation and local injections of misonidazole

Abstract

The radiosensitizing effect of misonidazole is dose dependent, so theoretically it would be desirable to use as large a dose as possible. However, clinical studies have indicated a maximum tolerable dose restricting the effects of misonidazole in patients. We injected misonidazole directly into tumor tissues in combination with irradiation in an attempt to obtain a sufficiently high concentration in tumors while maintaining a low level in the blood. Concentration of the drug in tumor tissues was confirmed to be high by examination of the resected low-grade chondrosarcoma into which the drug had been locally injected prior to the operation. Blood levels were confirmed to be significantly low. Seventeen patients were treated with local injections of the drug, each with radiotherapy. All patients either had advanced tumors, or were in the terminal stage after repeated radiotherapy and chemotherapy. A relatively high radiation dose per fraction was used. Complete response was obtained in eight patients (47%) and partial response in four (24%). No change was observed in three patients (18%) while two (12%) exhibited progressive disease. In the seven patients with multiple metastatic lesions, the response of the tumors treated with this method were compared to that of the tumors treated by radiation alone in the same patient. The sensitizing effect of the drug was clearly observed in three out of seven patients. No toxicities in the nervous system or in the gastrointestinal system were observed, and no local skin damage by the injections was seen. Local injections of misonidazole were shown to have a significant radiosensitizing effect without any side effects. The combined treatment of radiation and local injections of misonidazole is considered to be a promising new treatment method.