Arabinofuranosyl-5-azacytosine: activity against human tumors in athymic mice.

Arabinofuranosyl-5-azacytosine (Ara-AC), a new compound structurally related to arabinofuranosylcytosine (Ara-C) and 5-azacytidine (5-AC), has demonstrated significant therapeutic activity against a wide spectrum of murine tumors and three human tumor xenografts in the NCI tumor panel. Studies on the activity of Ara-AC in these and other human tumor xenograft models were undertaken to define its potential anti-human-tumor profile more completely. Ara-AC demonstrated marked antitumor activity against human tumor xenografts, including leukemias and solid tumors that do not respond to Ara-C or 5-AC. An important finding was the demonstration that Ara-AC was as effective by the oral route as when given intraperitoneally. Furthermore, the compound demonstrated synergism when combined with cisplatin in the treatment of refractory solid tumors and also induced monocyte-type differentiation of promyelocytic leukemia (HL-60) cells in vitro. Ara-AC is a promising new compound that may have utility in the treatment of human cancer beyond that anticipated for a cytotoxic nucleoside.