CLONOGENIC SURVIVAL STUDIES OF HUMAN COLON-TUMOR CELL-LINES IN-VITRO - COMBINED HYPERTHERMIA, 5-FLUOROURACIL LEUCOVORIN, CARBOPLATIN AND TUMOR-NECROSIS-FACTOR

The responses of DLD-1 and HCT-15 human colon adenocarcinoma cells to hyperthermia, 5-fluorouracil (5-FU)/leucovorin, carboplatin and tumor necrosis factor-alpha, singly and in multiple combinations, were evalu ated in clonogenic assays. The combination of hyperthermia with the lo wer dose combination resulted in a survival fraction of about 0.005 to 0.001 for both cell types, whereas estimated additive interactions al one would have resulted in a survival fraction of about 0.5 (DLD-1) or 0.05 (HCT-15), A survival fraction of 0.00001 or greater was observed when the higher dose levels were combined with hyperthermia, whereas additive interactions alone would have achieved a decrease of only 0.0 01 or 0.0001 in the surviving fraction. The combination of the three o ther modalities at either dose level under conditions of hyperthermia or normothermia achieved statistically significant apparently supra-ad ditive losses of clonogenicity in HCT-15 cells; similar results were o btained with the lower dose level in DLD-1 cells. Our results suggest that human colon tumor cells are markedly sensitive to this combinatio n of modalities when used at clinically achievable dose levels.