Summary of studies adding systemic chemotherapy to local hyperthermia and radiation.

The Joint Center-MIT group sought to maximize the efficacy of hyperthermia plus radiation by adding systemic anticancer drugs chosen in the laboratory. After extensive laboratory investigations utilizing primarily the FSaIIC murine fibrosarcoma, we determined that cisplatin was the best drug with which to begin clinical testing and that the sequence cisplatin-->hyperthermia-->radiation was most efficacious. A clinical experience was then gained which found that: (1) the tolerable doses of cisplatin weekly x 6 used with local hyperthermia and radiation (limited by bone marrow suppression) were 50 mg/m2 weekly in chemotherapy naive patients and 30 mg/m2 weekly in patients having had extensive prior drug treatment, (2) apparent complete response occurred in about 50% of patients, and (3) tumour lysis necessitating surgical repair occurred predominantly in patients with recurrent breast cancer in previously heavily irradiated fields where an incidence of 38% was observed as opposed to only 6% in breast cancer patients having had no prior radiation. In an attempt to further improve the local control potential of the combination we tested the addition of other anticancer drugs in the laboratory. Our findings were that both mitomycin C and etanidazole were far better than other agents and were able to double the tumour growth delay produced by the cisplatin/heat/radiation trimodality treatment. Since etanidazole is not marrow suppressive, clinical testing of etanidazole in the trimodality setting along with cisplatin/heat/radiation has been initiated.