ABSENCE OF WHOLE-BODY HYPERTHERMIA EFFECT ON CISPLATIN DISTRIBUTION IN SPONTANEOUS CANINE TUMORS

Purpose: This study was conducted to evaluate the effect of whole body hyperthermia (WBH) on cisplatin (CDDP)-derived platinum (Pt) disposit ion in tumor and normal tissue in dogs with spontaneously arising neop lasia undergoing conventional pretreatment diuresis. Methods and Mater ials: Cisplatin was administered to 12 dogs with terminal stage, metas tatic neoplasia. Cisplatin (50 mg/M(2) over 1 h) was administered foll owing 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 temperatur e x 90 min) simultaneously with CDDP infusion. Dogs were euthanized fo llowing the CDDP infusion, and samples from critical organs, tumor, an d normal tissue adjacent to the tumor were immediately collected. Resu lts: No significant differences existed between groups in serum or nor mal tissue Pt content. Thirty-eight tumor samples were obtained from 2 7 tumors in the six dogs included in the normothermic group and 43 tum or samples were obtained from 29 tumors in the six dogs undergoing WBH , Tumor volume varied from 0.08 cm(3) to 2270 cm(3) and multiple sampl es were obtained from tumors greater than 3 cm in diameter, Twenty-fiv e paired tissue samples of tumor and adjacent normal tissue were colle cted from dogs in the normothermic group and 31 paired samples were ob tained from the hyperthermic group, No differences were observed betwe en groups in tumor Pt content or in the tumor/normal tissue Pt ratios. Conclusion: Pt disposition was unaffected by WBH under conditions rep orted in this study, A forced diuresis is necessary to clinically admi nister CDDP at maximally tolerable doses, This maneuver results in inc reased blood flow to critical normal tissue that seemingly obviates an y hyperthermia-induced alterations in drug disposition.