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Effect of Drug Exposure Duration and Sequencing on Hyperthermic Potentiation of Mitomycin-C and Cisplatin¹

Department of Radiation Oncology, University of California, San Francisco, California 94143

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°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.

¹ This work was supported in part by Grants CA-31397 and CA-09215 from the National Cancer Institute, Department of Health, Education, and Welfare.

² To whom requests for reprints should be addressed, at Dept. of Radiation Oncology, Long Hospital, Room L-75, University of California, San Francisco, CA 94143.

Received 8/ 5/86. Revised 9/26/86. Accepted 10/ 3/86.