Stewart F A, Oussoren Y, Bartelink H
Experimental Therapy, Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
Radiother Oncol. 1989 May;15(1):93-102. doi: 10.1016/0167-8140(89)90122-9.
The aim of these studies was to measure the extent of renal damage after fractionated irradiation in combination with cis-diamminedichloroplatinum(II) (c-DDP) and to determine whether there was any drug-induced inhibition of repair of sublethal X-ray damage. Fractionated irradiations were given either in a short overall treatment time of 2 days or in a total time of one month, in which irradiations were given in the first and fourth weeks only. A single dose of c-DDP was given before the first X-ray dose for treatments in a total time of 2 days and before the first X-ray dose of each week for the split-course treatments. Renal function was measured at monthly intervals (from 18 to 39 weeks after the start of treatment) by clearance of 51Cr-EDTA. The renal damage was always worse after combined treatments (X + c-DDP) than after X-rays alone. A comparison of radiation dose-response curves with and without c-DDP yielded Dose Enhancement Factors (DEFs) of 1.2 to 1.4 for all fractionation schedules, with no trend for an increase in DEF with increasing number of fractions. A Linear-Quadratic (LQ) analysis of the data demonstrated that there was no change in the alpha/beta value for renal radiation damage for the combined treatments compared with X-rays alone (alpha/beta = 2-3 Gy). These results suggest that the increased renal damage which occurred after combined X + c-DDP was due to independent, additive toxicities and not to radiosensitization or inhibition of X-ray repair by the drug.
这些研究的目的是测量分次照射联合顺二氯二氨铂（II）（c-DDP）后肾脏损伤的程度，并确定是否存在药物诱导的亚致死性X线损伤修复抑制。分次照射的总治疗时间为2天或1个月，其中仅在第1周和第4周进行照射。对于总治疗时间为2天的治疗，在首次X线照射前给予单次剂量的c-DDP；对于分割疗程治疗，在每周的首次X线照射前给予单次剂量的c-DDP。在治疗开始后的每月间隔（18至39周）通过51Cr-EDTA清除率测量肾功能。联合治疗（X + c-DDP）后的肾脏损伤总是比单纯X线照射后的更严重。对有和没有c-DDP的辐射剂量反应曲线进行比较，所有分割方案的剂量增强因子（DEF）为1.2至1.4，且DEF没有随分次次数增加而增加的趋势。对数据进行线性二次（LQ）分析表明，与单纯X线照射相比，联合治疗的肾脏辐射损伤的α/β值没有变化（α/β = 2 - 3 Gy）。这些结果表明，X + c-DDP联合治疗后发生的肾脏损伤增加是由于独立的、累加的毒性作用，而非药物的放射增敏作用或对X线修复的抑制作用。
