Comparison of 1-(2-deoxy-2-fluoro-4-thio-β-d-arabinofuranosyl)cytosine with gemcitabine in its antitumor activity

The antitumor activity of a novel nucleoside, 1-(2-deoxy-2-fluoro-4-thio-β-d arabinofuranosyl)cytosine (4′-thio-FAC) was compared with that of 2′-deoxy-2′,2′-difluorocytidine (gemcitabine). 4′-Thio-FAC showed potent antitumor effects against various solid cancer cell lines in vitro. Also, gemcitabine showed remarkable in vitro antitumor effects, even more potent than 4′-thio-FAC. However, 4′-thio-FAC inhibited tumor growth more strongly than gemcitabine did at the same dose against human cancer cells implanted s.c. in nude mice. In addition, 4′-thio-FAC suppressed the tumor growth by oral administration. The toxicity of 4′-thio-FAC was weaker than that of gemcitabine in nude mice in both consecutive and intermittent administration. Accordingly, clinical usefulness of 4′-thio-FAC is expected.