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Potential for Therapy of Drugs and Hyperthermia¹

Department of Radiology, Stanford University School of Medicine, Stanford, California 94305

The interaction of hyperthermia (41–45°C) and chemotherapeutic agents frequently results in increased cytotoxicity over that predicted for an additive effect, although to date only a very limited number of drugs have been examined for such a possible interaction. At 42°C, the upper limit of temperature useful for whole-body hyperthermia, the most promising agents of those examined to date appear to be the nitrosoureas and cis-platinum. Insufficient data exist for cyclophosphamide, whose long plasma half-life makes it an attractive candidate. Localized heating seems optimum at higher temperatures (43–45°C). At these temperatures, not only those drugs effective at 42°C but particularly bleomycin and possibly amphotericin B become candidates. No data exist in the literature on possible "thermic sensitizers," i.e., drugs which are noncytotoxic at 37°C but which become effective at elevated temperatures. Two special cases are Adriamycin and actinomycin D. These drugs may be contraindicated for clinical use, since not only synergism but also protection by hyperthermia have been demonstrated, depending upon the time-sequence relationships of the heat and drug treatments.

¹ Presented at the Conference on Hyperthermia in Cancer Treatment, September 15 and 16, 1978, San Diego, Calif. Supported by USPHS Grants CA-15769 and CA-19386.