Arabinosylcytosine (ara C) and 2,2' anhydro arabinosyl 5 fluorocytosine (AAFC) in the treatment of acute leukemia

1 β D arabinofuranosyl cytosine (ara C) was first used in clinical neoplastic disease in 1963 with results that were somewhat disappointing (1). Three different approaches have improved these results and made this drug the mainstay of the treatment of acute myeloblastic leukemia (AML) for the past ten years:. Continuous i.v. administration (5) or single injections every eight or every twelve hours for five to eight days. The search for combinations potentiating the effect of ara C in mouse leukemia suggested that cyclophosphamide and ara C (3,4) or thioguanine and ara C (6), might be better than ara C alone and these combinations led to the cytoxan, vincristine, ara C and prednisone program (COAP) of Frei and Freireich (5), to Daunomycin followed by continuous ara C for five to seven days by Holland and his group, Adriamycin followed by continuous ara C for seven to nine days by McCredie et al. (7), and the L 6 protocol of Clarkson et al. (8) where ara C and thioguanine are given every twelve hours for courses lasting seven to ten days approximately every four weeks followed by a complex maintenance regimen. New derivatives were synthesized and tested against mouse leukemia in vitro and in vivo. Recently, two cyclic derivatives, 2,2' anhydro arabinosylcytosine (cyclocytidine) and 2,2' anhydro arabinosyl 5 fluoro cytosine (AAFC), have been shown to be superior to ara C in mouse leukemia in vivo and to be active both intraperitoneally and by mouth by single as well as by daily doses and against the intracerebrally inoculated leukemia as well as leukemia inoculated intraperitoneally.