OPTIMUM FRACTIONATION OF C3H MOUSE MAMMARY-CARCINOMA USING X-RAYS, HYPOXIC-CELL RADIOSENSITIZER RO-07-0582, OR FAST-NEUTRONS

Experiments extending over several years were completed in which local control of mammary tumors in C3H mice was compared with acute skin reactions in other mice for a number of fractionated X-ray and fast neutron schedules. Two types of fractionated treatment were investigated: short overall times of up to 4 days and longer overall times of 9-18 days. The effectiveness of each schedule was estimated by comparing the local tumor control that could be achieved for a given skin reaction. In the short treatment schedules, the extent of tumor control was very variable, ranging from poor to good. It was critically dependent on fraction size and on the interval between fractions in a way that was consistent with reoxygenation in the tumor being the crucial factor. In the longer treatment schedules, fraction size and interval were not so critical and overall time was the governing factor; too long overall times yielded poor results because proliferation in the tumor was faster than in skin. In the short, variable type of treatment it was shown that poor results using X-rays could be improved, to about the same level as the best X-ray results, by using either the specific hypoxic-cell radiosensitizing drug Ro-07-0582 [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] with X-rays, or by using cyclotron-produced fast neutrons. These observations support the concept of hypoxia and reoxygenation being the crucial factors in short treatment schedules.