Enhancement of the in vivo antitumor activity of clofarabine by 1-β-d-[4-thio-arabinofuranosyl]-cytosine

Purpose Clofarabine increases the activation of 1-β-d-arabinofuranosyl cytosine (araC) in tumor cells, and combination of these two drugs has been shown to result in good clinical activity against various hematologic malignancies. 1-β-d-[4-thio-arabinofuranosyl] cytosine (T-araC) is a new cytosine analog that has exhibited excellent activity against a broad spectrum of human solid tumors and leukemia/lymphoma xenografts in mice and is currently being evaluated in patients as a new drug for the treatment of cancer. Since T-araC has a vastly superior preclinical efficacy profile in comparison to araC, we have initiated studies to determine the potential value of clofarabine/T-araC combination therapy.