Page R L, Lee J, Riviere J E, Dodge R K, Thrall D E, Dewhirst M W
Department of Companion Animals and Special Species, North Carolina State University, College of Veterinary Medicine, Raleigh, USA.
Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1097-102. doi: 10.1016/0360-3016(94)00483-2.
This study was conducted to evaluate the effect of whole body hyperthermia (WBH) on cisplatin (CDDP)-derived platinum (Pt) disposition in tumor and normal tissue in dogs with spontaneously arising neoplasia undergoing conventional pretreatment diuresis.
Cisplatin was administered to 12 dogs with terminal stage, metastatic neoplasia. Cisplatin (50 mg/M2 over 1 h) was administered following 4 h of forced fluid diuresis (0.9% saline at 10 ml/kg/h). Six of the 12 dogs underwent a WBH procedure (42 degrees C rectal temperature x 90 min) simultaneously with CDDP infusion. Dogs were euthanized following the CDDP infusion, and samples from critical organs, tumor, and normal tissue adjacent to the tumor were immediately collected.
No significant differences existed between groups in serum or normal tissue Pt content. Thirty-eight tumor samples were obtained from 27 tumors in the six dogs included in the normothermic group and 43 tumor samples were obtained from 29 tumors in the six dogs undergoing WBH. Tumor volume varied from 0.08 cm3 to 2270 cm3 and multiple samples were obtained from tumors greater than 3 cm in diameter. Twenty-five paired tissue samples of tumor and adjacent normal tissue were collected from dogs in the normothermic group and 31 paired samples were obtained from the hyperthermic group. No differences were observed between groups in tumor Pt content or in the tumor/normal tissue Pt ratios.
Pt disposition was unaffected by WBH under conditions reported in this study. A forced diuresis is necessary to clinically administer CDDP at maximally tolerable doses. This maneuver results in increased blood flow to critical normal tissue that seemingly obviates any hyperthermia-induced alterations in drug disposition.
本研究旨在评估全身热疗（WBH）对患有自发性肿瘤且正在接受常规预处理利尿的犬类肿瘤组织和正常组织中顺铂（CDDP）衍生铂（Pt）分布的影响。
对12只患有晚期转移性肿瘤的犬类给予顺铂。在强制液体利尿4小时（0.9%生理盐水，10 ml/kg/h）后，给予顺铂（50 mg/M²，持续1小时）。12只犬中有6只在输注CDDP的同时接受WBH程序（直肠温度42摄氏度，持续90分钟）。在输注CDDP后对犬实施安乐死，并立即收集关键器官、肿瘤以及肿瘤相邻正常组织的样本。
两组血清或正常组织中的Pt含量无显著差异。在体温正常组的6只犬的27个肿瘤中获取了38个肿瘤样本，在接受WBH的6只犬的29个肿瘤中获取了43个肿瘤样本。肿瘤体积从0.08 cm³到2270 cm³不等，从直径大于3 cm的肿瘤中获取了多个样本。在体温正常组的犬中收集了25对肿瘤与相邻正常组织的组织样本，在热疗组中获取了31对样本。两组在肿瘤Pt含量或肿瘤/正常组织Pt比值方面未观察到差异。
在本研究报告的条件下，WBH不影响Pt的分布。为了临床以最大耐受剂量给予CDDP，强制利尿是必要的。这种操作会增加关键正常组织的血流量，这似乎消除了热疗引起的药物分布变化。
