Optimal scheduling increases therapeutic gain of adriamycin combined with hyperthermia

To maximize the thermal enhancement of antitumor effect and minimize normal tissue damage, the timing of Adriamycin (ADM) administration in relation to hyperthermia was examined. Tumor growth of a subcutaneously transplanted fibrosarcoma as well as damage in normal tissues were measured in F344 rats treated with variable schedules of ADM and hyperthermia. Simultaneous application of 5 mg/kg i.v. of ADM with hyperthermia (120 min at 41.5 degrees C) resulted in a synergistic antitumor effect, but there was no thermal enhancement of the antitumor activity when 2.5 mg/kg ADM was given. Thermal enhancement of the antitumor effect induced by 5.0 mg/kg ADM was greater when ADM was given 30 min before or just prior to hyperthermia compared to that given during hyperthermia. ADM given prior to hyperthermia caused less damage to normal tissue than that given during hyperthermia, as evidenced by a prolonged survival and lower incidence of ascites and tendency to bleed. Thus ADM administration 30 min before or just prior to hyperthermia resulted in greater therapeutic gains than ADM given during hyperthermia. In the light of these results, the optimal scheduling of administration of ADM with hyperthermia is important for a therapeutic gain for cancer patients.