Effects of alpha-difluoromethylornithine alone and combined with adriamycin or vindesine on L1210 leukemia in mice, EMT6 solid tumors in mice, and solid tumors induced by injection of hepatoma tissue culture cells in rats.

The effects of alpha-difluoromethylornithine (DFMO; RMI 71782) in combination with vindesine or Adriamycin were investigated in three different animal tumor models. When given in a concentration of 2% in drinking water to C57BL/6 X DBA/2 F1 mice inoculated i.p. with L1210 leukemia cells, DFMO prolonged the survival time 1,2-fold. Treatment with vindesine (0.1 mg/kg/week i.p. or Adriamycin (2.5 mg/kg/week i.p.) increased the mean survival time 1.4- and 2.3-fold, respectively. DFMO with vindesine doubled survival time, while DFMO with Adriamycin increased it 3.5-fold and yielded 30% long-term survivors. The growth of solid tumors induced in Buffalo rats by i.m. injection of hepatoma tissue culture cells was inhibited 65% after 2 weeks of DFMO treatment. Similar inhibition of growth could be achieved by weekly i.p. injections of vindesine (0.2 mg/kg) or Adriamycin (2.5 mg/kg). When the same doses of these drugs were administered in combination with DFMO, the growth of this hepatoma was completely arrested. Combined treatment of BALB/c mice bearing s.c. solid EMT6 tumors with DFMO and adriamycin or vindesine also resulted in enhanced inhibition of tumor growth compared to single-drug therapy. These results indicate that combination of DFMO with vindesine or Adriamycin is an effective approach to the treatment of several animal cancers.