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Activity of 2-Fluoro-5-methylarabinofuranosyluracil against Mouse Leukemias Sensitive to and Resistant to 1-ß-D-Arabinofuranosylcytosine¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021

A new pyrimidine nucleoside, 2'-fluoro-5-methyl-1-ß-D-arabinofuranosyluracil, previously has been shown to be active against the herpes group of viruses in vitro and in vivo. It is also active against mouse and human leukemic cells in culture and against mouse leukemias L1210, P388, and P815 in vivo. In contrast to other 1-ß-D-arabinofuranosylcytosine (ara-C) derivatives, 2'-fluoro-5-methyl-1-ß-D-arabinofuranosyluracil, when given either i.p. or p.o., is highly active against lines of leukemias P815 and L1210 made resistant to ara-C. Against P815/ara-C and L1210/araC, it is more effective than is 5-azacytidine, a drug which has shown definite effectiveness in patients with acute leukemia whose disease has become resistant to ara-C. For these reasons, 2'-fluoro-5-methyl-1-ß-D-arabinofuranosyluracil would seem to merit clinical trial in patients with acute nonlymphocytic leukemia whose disease has become resistant to ara-C.

¹ This work was supported by American Cancer Society Grant CH-27W; National Cancer Institute Grants CA-05826, CA-08748, CA-16534, CA-18601, CA-18856, and CA-27569; and the Hearst Foundation.

² To whom requests for reprints should be addressed.

Received 10/ 5/81. Accepted 3/30/82.