Effect of drug exposure duration and sequencing on hyperthermic potentiation of mitomycin-C and cisplatin.

The effects of drug exposure duration and of heat and drug sequencing on hyperthermic potentiation of mitomycin-C (MMC) and cisplatin (DDP) were studied. Heating for 1 h at 42 degrees C was combined with drug exposure times of 1, 2, 4, or 8 h. For both DDP and MMC, hyperthermic potentiation was greatest when heating was done during drug exposure. Dose enhancement ratios for both drugs at 1% survival were highest with the shortest drug exposure times and decreased as the drug exposure time increased from 1 to 8 h. For DDP, the dose enhancement ratio decreased from 1.9 with a 1-h drug exposure to 1.2 with an 8-h drug exposure. For MMC, the dose enhancement ratio decreased from 1.8 to 1.5 as the drug exposure duration was increased from 1 to 8 h. Our results suggest that thermochemotherapy in vivo is likely to be most effective with rapid infusions of DDP or MMC.