MULTI-CHEMOTHERMOIMMUNOTHERAPY FOR HUMAN COLON ADENOCARCINOMA IN-VITRO

Effective adjunctive therapies for colorectal carcinoma are clearly ne eded. We evaluated the cytotoxic responses in vitro of human colon car cinoma cell lines to combined modalities: 5-fluorouracil/leucovorin (5 -FU/LV), carboplatin (CP), tumor necrosis factor (TNF) and hyperthermi a (HTX). Cytotoxicity was evaluated in a cell proliferation assay usin g crystal violet staining. 5-FU/LV was administered 2-3 days before TN F and CP, followed 1 h later by HTX. These cell lines were relatively resistant to HTX alone (42 degrees C for 2 h), but were heterogeneous in their responses to various doses of the other single agents. This h eterogeneity was also evident for combined modalities: the HCT-15 cell . line exhibited significant supra-additivity for selected doses of CP , TNF and 5-FU/LV, which was further enhanced by hyperthermia. In cont rast, the HT-29 cell line did not demonstrate a strong pattern for sup ra-additivity, whereas the DLD-1 cell line had an intermediate respons e. Thus, our results suggest one approach to develop effective and dos e-sparing multimodality therapeutic regimens for colon adenocarcinoma.