Combination effects of Ara-C and 5-fluorodeoxyuridine against leukemia cells in vitro and in mice.
BACKGROUND
Ara-C (1-beta-D-arabinofuranosylcytosine) is widely used for treatment of human leukemia. However, due to emergence of resistance, new drug combinations need to be developed.


METHODS
We tested the combination of Ara-C with 5-FdUrd (5-fluorodeoxyuridine) in L1210 and P388D1 mouse leukemia cells in vitro and in vivo by growth inhibition and recovery assay in leukemia-bearing mice.


RESULTS
Simultaneous incubation of cells with Ara-C and 5-FdUrd yielded more than additive effects for most combinations in both cell lines; synergy was seen in P388D1 cells. P388D1 cells showed delayed growth after treatment with Ara-C or 5-FdUrd in a growth recovery assay. In animal studies, simultaneous subcutaneous administration of the compounds did not show any significant beneficial effects as compared with monotherapy. Intraperitoneal administration of both compounds, however, significantly prolonged the survival of P388D1 animals.


CONCLUSIONS
Depending on cell type and route of drug administration, the combination of Ara-C and 5-FdUrd might offer a promising additional treatment option for leukemia.
Rauko
Peter
P
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
Bauer
Wolfgang
W
Horvath
Zsuzsanna
Z
Höchtl
Thomas
T
Saiko
Philipp
P
Karl
Doris
D
Schott
Herbert
H
Fritzer-Szekeres
Monika
M
Novotny
Ladislav
L
Szekeres
Thomas
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
D005467:Floxuridine; D003561:Cytarabine