Early and late effects of cisplatin and radiation at acute and low dose rates on the mouse skin and soft tissues of the leg.

The influence of radiation dose rate and drug dose on the combined effects of cisplatin (Cis-diamminedichloroplatinum (II] and radiation on the skin and soft tissues was studied in the C3Hf/SED mice. Localized acute-dose-rate irradiation (ADRI) at 3.345 Gy/min and continuous low-dose-rate irradiation (CLDRI) of the hind leg at 0.028 Gy/min with and without the drug was delivered using a 137Cs laboratory irradiator. Cisplatin at 6 or 11 mg/kg was given by intraperitoneal bolus injection 1 hour before ADRI or by continuous infusion during CLDRI. Acute skin reaction was scored from days 13 to 30 and late skin contraction and leg contracture were measured at days 90, 180, 270, and 360 after treatment. A marked dose-rate effect was observed for these early and late normal tissue endpoints. At a dose of 60 Gy of CLDRI, the dose rate factor (DRF = isoeffect dose at CLDRI/isoeffect dose at ADRI) was 1.82 for acute skin reaction and 1.76 for late skin contraction or leg contracture at day 270. However, there was no significant enhancement of these early and late normal tissue effects by cisplatin at 6 or 11 mg/kg at either acute or low dose rates. Thus neither drug dose nor radiation dose rate had a significant impact on the combined effects of cisplatin and radiation on the mouse skin and soft tissues of the leg.