Sequencing of trimodality therapy [cis-diamminedichloroplatinum(II)/hyperthermia/radiation] as determined by tumor growth delay and tumor cell survival in the FSaIIC fibrosarcoma.

In order to improve local control of tumors over that achievable with local hyperthermia and radiation, we are testing the use of systemic cis-diamminedichloroplatinum(II) (CDDP) in conjunction with the other two modalities. In the FSaIIC fibrosarcoma, growth delay experiments indicated that the use of any two modalities resulted in at least additive effects on growth delay. When the trimodality treatment was tested, the sequence CDDP followed by hyperthermia followed by X-ray produced a growth delay of approximately 25 days which was superior to the growth delay produced by the sequences CDDP, X-ray, and hyperthermia (19 days) and X-ray, CDDP and hyperthermia (14 days). In excision experiments, also performed in the FSaIIC tumor system, we again observed clearly superior cytotoxicity in the sequence CDDP, hyperthermia, and X-rays over the other sequences tested. Our results indicate that scheduling CDDP just prior to heating and following the heat treatment with the radiation fractions results in the best tumor cell kill, probably because this sequence takes maximum advantage of the radiosensitizing properties of the combined heat-CDDP treatment. In addition, the strong cytotoxic interaction between CDDP and hyperthermia is also optimized by this scheduling. We believe these results have significant clinical implications.