The Response of a Transplantable Tumor to Fractionated Irradiation: III. Fast Neutrons Plus the Radiosensitizer Ro-07-0582

The response of a transplantable mammary carcinoma in CBA mice has been assessed using delay in tumor growth after irradiation. Dose-response curves have been obtained for tumors treated with single doses or with two or five fractions of cyclotron neutrons, given in the presence or absence of the hypoxic cell radiosensitizer Ro-07-0582. The results are compared with previously published X-ray data. A greater delay in tumor growth was observed for all treatments if the radiosensitizing drug was present. A radiation dose reduction factor (DRF) could be measured from the pairs of dose-response curves. The factor was 1.2 to 1.4 for single doses and 1.1 to 1.3 for two and five fractions when 0.67 mg/g of the drug was used before each irradiation. The effect of a smaller drug dose (0.15 mg/g) was tested with a single dose of neutrons and a smaller effect was observed (DRF = 1.1). These results, together with those of papers I and II, show that all three methods of overcoming the resistance of hypoxic cells (fractionation, radiosensitizers, fast neutrons) are effective, but less than optimal if used individually. Any combination of the three increases the therapeutic effectiveness. The most effective treatment tested, with this tumor, was five fractions of neutrons plus the radiosensitizer Ro-07-0582.