The effect of cis-diamminedichloroplatinum(II) on radiation damage in mouse rectum after fractionated irradiation.

The influence of cis-diamminedichloroplatinum(II) (c-DDP) on radiation injury in the rectum of mice was investigated after single dose and fractionated irradiation. Mice were exposed to single doses, or 2, 4 or 8 fractions of X-rays given daily (or twice a day for the 8 fractions) with or without 8 mg/kg of c-DDP. The incidence of rectal stenosis and of anal discharge were scored and a direct analysis of the data for linear-quadratic dose-dependence of damage was performed with correction for censoring. For each endpoint, c-DDP did not significantly change the dose-response curves after fractionated irradiation. Subtile modifications in the coefficients of the linear-quadratic relationship were observed. The drug appeared to increase the alpha term by a factor of 2.3 and the beta term by a factor of 1.5, but the differences did not reach statistical significance. For the rectal stenosis endpoint, the alpha/beta was 4.4 Gy after irradiation alone and 6.9 Gy after combination treatment. Again the differences were not significant. These data suggest that c-DDP did not reduce the repair capacity in the mouse rectum during fractionated irradiation. Combined modality therapy with c-DDP and radiation would therefore not be expected to cause an increase in late damage in the large bowel.