N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (
PLAC) was administered PO to 76 patients with acute
leukemia,
myelodysplastic syndromes (MDSs), and
myeloproliferative disorders (MPDs). Of 20 patients with
acute myelogenous leukemia, 2 achieved complete remission, and the only patient with
acute lymphoblastic leukemia achieved partial remission. Remission was reached with
PLAC 100-300 mg/day 25-66 days after the start of
therapy. Among 22 patients with MDS, 1 patient achieved a good response and 8 achieved partial response. Responses were reached with
PLAC 50-200 mg/day 7-153 days (median, 33 days) after the start of
therapy. Improvement of
polycythemia was observed in all 5 patients with
polycythemia vera, and reduction of
thrombocytosis was observed in 5 out of 6 patients with
essential thrombocythemia and
myelofibrosis. An antileukemia effect was noted in 1 of 5 with
chronic myelogenous leukemia. Major side effects were gastrointestinal toxicities and myelosuppression. In spite of the disadvantages, such as unpredictable absorption and a lower response rate to acute
leukemia compared with its parent compound, this antileukemia
Ara-C analogue that is administrable PO will be useful in the treatment of MDSs and MPDs, which do not necessarily require admission to hospital, and in the treatment of acute
leukemia of the aged, a condition for which intensive
chemotherapy is not appropriate.