Misonidazole in fractionated radiotheraphy of a murine mammary carcinoma: Comparison of tumor and normal tissue response

Abstract

The potential therapeutic benefit of misonidazole was tested in radiotherapy with 1, 2, 5, and 10 equal fractions, using as endpoints local tumor control (TCD50) of murine mammary carcinoma MDAH-MCa-4 and leg contracture at the TCD50, measured 120 days after irradiation. In controls and misonidazole-treated mice, the TCD50 increased with the number of fractions, from 66.7 to 114.6 Gy in controls, and from 43.3 to 75.7 Gy with misonidazole. At doses of ≥0.1 mg/g body weight, misonidazole reduced the TCD50 in all fractionation schedules; however, because of toxicity, 1.0 and 0.6 mg/g could be given with only 1 or 2 fractions. Leg contracture at the TCD50 was greatest (14.5 mm) in control mice treated with a single dose of radiation, and was least (7.2 to 7.4 mm) in those treated with a single dose of radiation preceded by 1.0 or 0.6 mg misonidazole/g body weight. With 0.1 mg misonidazole/g, the leg contracture at the TCD50 was less (9.8 to 12.2 mm with the various schedules) than in controls (12.0 to 14.5 mm) for 1, 5, or 10 fractions. Therefore, a therapeutic gain could be obtained by using misonidazole with 1, 2, 5, or 10 fractions, but the greatest gain occurred with 1 fraction, with high doses of misonidazole, that is, 0.6 to 1.0 mg/g.