The effect of misonidazole in combination with radiation dose fractionation.

Single doses or multiple fractions of 2, 3, 5 or 10 Gy were given daily to KHT Sarcomas, growing in C3H mice, in combination with a misonidazole dose of 0.5 mg/g body weight administered 30--40 min before each radiation dose. Cell survival assays were performed on groups of tumours after different total doses to determine tumour cell survival curves for each fractionation schedule. The results indicate that misonidazole is effective in sensitizing the tumours to single doses and to large dose fractions, but that the degree of sensitization declines with fraction size such that there is no difference between the survival curves obtained for 2 Gy fractions given with or without prior drug treatment. Comparison of iso-effect curves, derived from the data, with those for normal skin suggests that, even though misonidazole increases the effect of the radiation on the tumour when large dose fractions are used, the small dose fractions probably still give a better "therapeutic ratio".