CHRONIC EFFECT OF WHOLE-BODY HYPERTHERMIA COMBINED SIMULTANEOUSLY WITH CIS-DIAMINEDICHLOROPLATINUM(II) ON NORMAL TISSUE IN RAT

Long-term effects of cisplatin (DDP) (6 mg/kg) alone at 37 degrees C a nd DDP (2 mg/kg) plus whole body hyperthermia 120 min at 41.5 degrees C) on DDP-mediated normal tissue toxicities were compared up to 12 mon ths post-treatment using a F344 rat model. Acute renal damage, represe nted by an increase in blood urea nitrogen (BUN) at day 5 posttreatmen t, was significantly higher after DDP (6 mg/kg) alone at 37 degrees C than the increase in BUN after DDP (2 mg/kg) plus whole body hyperther mia. After recovery, BUN levels as a result of both treatments remaine d elevated. From 9 months onwards BUN levels as a result of the combin ed treatment gradually increased to values > 100 mg/dl. At 12 months, side toxicities as a result of the combined treatment were more severe than the side effects noted after DDP (6 mg/kg) alone at 37 degrees C . Red blood cell and hematocrit values were significantly reduced, whe reas BUN was significantly increased. The results obtained with histol ogical examination of the kidneys corresponded with the observed funct ional differences. Platinum levels in the kidney, however, were highes t in the DDP (6 mg/kg) alone at 37 degrees C group. This observation d oes not explain why the chronic toxicity as a result of the combined m odality treatment was more severe.