Thiarabine has demonstrated exceptional antitumor activity against
numerous human tumor xenografts in mice, being superior to gemcitabine,
clofarabine, or cytarabine. Unlike cytarabine, thiarabine demonstrated excellent
activity against solid tumor xenografts, suggesting that this agent has the
kind of robust activity in animal models that leads to clinical utility.
Thiarabine is effective orally (bioavailability of approximately 16%) and with
once per day dosing: Two characteristics that distinguish it from cytarabine.
Although both the structure and basic mechanism of action of thiarabine are similar to that
of cytarabine, there are many quantitative differences in the biochemical pharmacology of these two agents
that can explain the superior antitumor activity of thiarabine. Two important attributes are the long retention
time of the 5’-triphosphate of thiarabine in tumor cells and its potent inhibition of DNA synthesis. The biochemical
pharmacology of thiarabine is also different from that of gemcitabine. Thiarabine has been evaluated
in three phase I clinical trials, where it has demonstrated some activity in heavily pretreated patients with hematologic
malignancies and solid tumors. Because of its impressive activity against numerous human tumor
xenografts in mice, its unique biochemical activity, and encouraging clinical results in phase I clinical trials,
we believe thiarabine should continue to be evaluated in the clinic for treatment of hematologic and/or solid
tumors. The preclinical results to date (superior in vivo antitumor activity, oral bioavailability, and once per
day dosing), suggest that thiarabine could replace cytarabine in the treatment of acute myelogenous leukemia.