The quantitative response of human tumours to radiation and misonidazole

Eleven patients with measurable subcutaneous or pulmonary metastases were selected for a study of the effectiveness of the radiosensitizer misonidazole (MIS). Evaluable data were obtained in 6 patients and radiosensitization demonstrated in 5. Patients were irradiated either before or after MIS, and each patient acted as his own control. Response to treatment in 5 cases was assessed in terms of growth delay, and radiation doses were selected in expectation of enhancement ratios of 1.2 to 1.5. In 1 case evidence of sensitization was obtained from differential tumour clearance from 2 areas of skin irradiated before or after MIS. Results in 4/5 growth-delay studies indicated enhancement ratios ranging from 1.1 to greater than 1.5. An enhancement ratio of 1.3 was measured in a case of squamous carcinoma treated by a 10-fraction course of irradiation. Evidence of sensitization was obtained in breast carcinoma, osteosarcoma, leiomyosarcoma, prostatic carcinoma and synoviosarcoma. The results of this study support the view that MIS may improve the radiotherapeutic management of a wide range of tumours, although more extensive data are required to identify those categories of disease in which greatest benefit will be obtained, and to indicate the optimum radiation schedule.