Stewart F A, Luts A, Oussoren Y, Begg A C, Dewit L, Bartelink H
Department of Experimental Radiotherapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Amsterdam.
NCI Monogr. 1988(6):23-7.
Functional kidney damage in mice was measured after bilateral irradiation with x-rays alone or in combination with cisplatin (c-DDP). A single drug dose (6 mg/kg) was injected 30 minutes before the first of four or eight x-ray doses, given as four fractions per day with a minimum interval of 5 hours between treatments. A 30-fraction schedule was also investigated, with 15 fractions given in the first week (3 fractions per day), followed by a 2-week rest period and another 15 fractions in the fourth week. The c-DDP (4 mg/kg) was administered 30 minutes before the first fraction of each week, giving a total drug dose of 8 mg/kg. Renal function was assessed monthly from 10 to 37 weeks after the start of treatment by the clearance of 51Cr-labeled EDTA. The combined treatment caused more kidney damage than either agent alone for all fractionation schedules. Enhancement of the radiation damage by c-DDP changed only slightly with fractionation; dose enhancement factors were 1.2 for 1 fraction to 1.3 for 30 fractions. Modeling studies showed that this was consistent with the additive toxic effects of the two agents. There was no change in the alpha/beta for renal damage after x-rays plus c-DDP, compared with x-rays alone (alpha/beta = 1.9 Gy), implying that there was no reduction in repair and no modification of the x-ray response by c-DDP.
在小鼠双侧接受单独X射线照射或联合顺铂（c-DDP）照射后，对其功能性肾损伤进行了测量。在给予四或八次X射线照射中的第一次照射前30分钟，注射单次药物剂量（6毫克/千克），每天分四次给予照射，每次照射之间的间隔至少为5小时。还研究了一种30次分割的方案，第一周给予15次分割（每天3次），随后休息2周，第四周再给予15次分割。在每周第一次分割前30分钟给予c-DDP（4毫克/千克），药物总剂量为8毫克/千克。在治疗开始后的10至37周内，每月通过51Cr标记的EDTA清除率评估肾功能。对于所有分割方案，联合治疗比单独使用任何一种药物造成的肾损伤都更严重。c-DDP对辐射损伤的增强作用随分割略有变化；剂量增强因子从1次分割时的1.2到30次分割时的1.3。模型研究表明，这与两种药物的相加毒性作用一致。与单独X射线照射相比（α/β = 1.9 Gy），X射线加c-DDP后肾损伤的α/β没有变化，这意味着修复没有减少，c-DDP也没有改变X射线反应。
