Optimal duration of whole body hyperthermia when combined with cis-diamminedichloroplatinum(II)

Abstract

We examined the optimal duration of whole body hyperthermia (WBH, 41.5 degrees C) when administered simultaneously with cis-diamminedichloroplatinum(II) (CDDP) using F344 rat fibrosarcoma model. The antitumor efficacy was measured by tumor growth delay (TGD) and nephrotoxicity was evaluated by the day 5 blood urea nitrogen (BUN) associated with different duration of WBH (0.5, 1, 1.5, 2 or 3 h) with a constant dose of CDDP (2 mg/kg i.v. bolus). There was significant increase in TGD from 2.8 days to 5.4 days when the WBH duration was increased from 0.5 to 1 h (p<0.001). CDDP-induced nephrotoxicity was also enhanced by WBH. We estimated specific therapeutic efficacy (STE) for each treatment using the ratio of antitumor effect measured by TGD to nephrotoxicity calculated from the degree of increment of BUN. CDDP combined with 1 h WBH produced the best STE of 2.2. We conclude, that to maximize the therapeutic gain, a 1 h duration is optimal in the present setting of thermochemotherapy.