Effects of 5-aza-2'-deoxycytidine in combination with the biochemical modulator thymidine or the immune modulator pyran copolymer on L1210 leukemia-bearing mice.

The purpose of these studies was to investigate the potential modulation by thymidine in vivo of the antitumor action of 5-aza-2'-deoxycytidine (DAC). During the course of these investigations it was observed that DAC given as a single dose to mice bearing late L1210 tumor resulted in cell kills estimated to be close to 6 logs. Because of the potentially large antigen load released by such a cell kill, the immune modulator pyran copolymer was also tested in combination with DAC. Thymidine increased the cytotoxicity of DAC but not in a selective fashion. Doses of DAC in combination with thymidine were more toxic to host mice than equivalent doses of DAC alone, but no therapeutic benefit was apparent with this combination at maximally tolerated doses. A single dose of pyran copolymer and DAC appears to result in an adjuvant action that eliminates the few remaining L1210 cells refractory to DAC chemotherapy. Doses of DAC alone that result in lengthy increases in survival times but no cures resulted in a substantial number of cures when used in combination with pyran copolymer.