In vivo response of murine RIF tumors to thermochemotherapy

The in vivo effects of hyperthermia combined with bleomycin, cis-platinum, or BCNU were studied. C3H mice with RIF tumors implanted on the dorsal aspect of their feet were used in these experiments. Heat alone (45 degrees C, 30 min) had a minimal effect on mean tumor growth delay (TGD), the time required for the tumor to reach twice the original tumor volume. The maximum tolerated dose (MTD), approximately equivalent to an LD10, of BCNU (50 mg/kg) gave a mean TGD of 24 days, while 40 mg/kg of BCNU (MTD for BCNU with heat) alone resulted in a mean TGD of only 5.5 days. No tumors were cured when treated with heat or chemotherapy alone. However, BCNU (40 mg/kg) given with concomitant heat (45 degrees C, 30 min) resulted in 9/12 cures (tumor control to 120 days). In the three remaining mice, there was one tumor growth, one foot amputation response and one death. The combinations of bleomycin-heat and cis-platinum-heat were inferior to BCNU-heat. Even the combination of bleomycin and cis-platinum with heat resulted in only 4/18 cures, with 5 tumor regrowths, 4 foot amputations, and 5 deaths. Thus, the combination of BCNU-heat gave the best in vivo response rate (75% cure) with acceptable toxicity.