Interaction of Heat with Radiation and Chemotherapy1

In using hyperthermia in the clinic, thermal dosimetry is essen tial and is discussed in terms of equating time-temperature relationships for an isoeffect to an equivalent time at a reference temperature, 43° for example. In applying time-temperatureequivalence, the sequence between heat and radiation and be tween two heat treatments, radiation dose rate, linear energy transfer, and physiological parameters must be considered. Fur thermore, thermal tolerance observed for both heat killing and heat radiosensitization, especially for doses of 400 rads or greater, may be considered as a thermal dose modifier. When hyperthermia is combined with drugs, most of the factors men tioned above are probably important and need careful evaluation, including the applicability of calculating equivalent time at a reference temperature. Examples are given for delayed heat sensitization after depletion of intracellular polyamines and for heat partially overcoming resistance to 1,3-bis-2-chloroethylnitrosourea in order to illustrate the importance of understanding heat effects on formation of reactive drug intermediates, perme ability of drugs into cells, and damage to target molecules.