Supraadditive effect of 2 ',2 '-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines

Purpose: This study assessed the cytotoxic effects of the nucleoside analog gemcitabine in combination with the diaminocyclohexane platinum compound o xaliplatin. Methods: Growth inhibition studies were performed using the hum an CEM leukemia cell line and the colon-cancer cell lines HCT 116 and Cole 320 DM. Gemcitabine-oxaliplatin combinations were compared with gemcitabine -cisplatin combinations in the same cell lines using similar experimental s ettings. Cells were exposed for 2 h to gemcitabine and then for 24 h to oxa liplatin or cisplatin, and vice versa. Results: The 50% inhibitory concentr ations (IC50 values) in single-drug experiments using 2 h of exposure to ge mcitabine and 24 h of exposure to oxaliplatin or cisplatin were, respective ly, 89 pM, 11.1 mu M, and 10.3 mu M for CEM cells; 46 pM, 10.2 mu M, and 2. 7 mu M for HCT 116 cells; and 102 pM, 4.6 mu M, and 8.6 mu M for Colo 320 D M cells. Gemcitabine-oxaliplatin combinations displayed supraadditive effec ts in human leukemia and colon-cancer cell lines. The sequence of gemcitabi ne followed by oxaliplatin was more effective than the opposite sequence in HCT 116 and Cole 320 DM colon-cancer cell lines. whereas the sequence of o xaliplatin followed by gemcitabine yielded to synergistic effects in CEM ce lls. The cytotoxic effects of gemcitabine-oxaliplatin combinations were bet ter than (HCT 116 cells) or equal to (CEM and Cole 320 DM cells) those of g emcitabine-cisplatin combinations. Conclusion: Our data show that the combi nation of gemcitabine with oxaliplatin exerts potent antiproliferative effe cts in human leukemia and colon cancer cells, warranting further investigat ions in the framework of phase I-II trials as an alternative for the treatm ent of solid malignancies.