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

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Abstract
The response of a transplantable mammary carcinoma in CBA mice was assessed using delay in tumor growth after irradiation. Dose-response curves were obtained for tumors treated with single doses or with 2 or 5 fractions of cyclotron neutrons, given in the presence or absence of the hypoxic cell radiosensitizer Ro-07-0582 [1-(2-nitro-(-imidazolyl)-3-methoxy-2-1 propanol]. 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 1.2-1.4 for single doses and 1.1-1.3 for 2 and 5 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 3 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 3 increases the therapeutic effectiveness. The most effective treatment tested, with this tumor, was 5 fractions of neutrons plus Ro-07-0582.