The interactions of
2-chlorodeoxyadenosine (2-CdA, cladribine) and three
anthracyclines:
doxorubicin (DOX),
idarubicin (IDA) and
mitoxantrone (MIT) were evaluated on murine
leukemias P388 and L1210. Prolongation of survival time of animals receiving drugs in combination compared to mice treated with drugs in monotherapy was tested. We have also evaluated interactions of the
cytostatics on murine
leukemias in vitro by measuring their inhibitory effects on P388 and L1210 cell proliferation. We have observed a synergistic effect of MIT and IDA in combination with 2-CdA on
P388 leukemia resulting in an increase of life span (ILS)=226% in case of MIT+2-CdA and ILS=126% in the case of IDA+2-CdA, whereas 2-CdA used as a sole
drug resulted in an ILS=47%. The survival time of animals inoculated with P388 leukemic cells and treated with DOX+ 2-CdA was similar to ILS gained by DOX monotherapy (178% and 200% respectively). The mice bearing
L1210 leukemia receiving combined
chemotherapy lived significantly longer than the animals on single agent regimens. The animals treated with schedule 2-CdA+MIT lived significantly longer (P=0.004) as compared to the groups receiving drugs in monotherapy (ILS of 2-CdA+MIT group=60%, ILS of MIT group 33%, and 2-CdA group 33%). Finally, combination of DOX or IDA with 2-CdA resulted in ILS =73% (2-CdA+DOX regimen), and ILS=60% in case of 2-CdA+IDA regimen, which is significantly higher than ILS gained on monotherapy schedules. In vitro tests revealed that all tested
anthracyclines enhance the antiproliferative activity of 2-CdA against L1210 and P388 leukemic cells (P<0.05). Our study has shown that all
anthracyclines potentiate 2-CdA antileukemic activity, both in vivo and in vitro. It failed however to point the best one to be combined with
cladribine. We suggests that further clinical trials with such combinations are needed.