RESPONSE TO CYTARABINE OCFOSFATE (YNKO1) IN A PATIENT WITH CHRONIC LYMPHOCYTIC-LEUKEMIA REFRACTORY TO TREATMENT WITH CHLORAMBUCIL PREDNISONE, FLUDARABINE, AND PREDNIMUSTINE/MITOXANTRONE/

Cytarabine ocfosfate (YNKO1) is a novel orally applicable prodrug of c ytosine arabinoside. Recent pharmacokinetic studies have revealed a pr olonged release of the cytotoxic agent cytosine arabinoside (araC) fro m hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic character istics of cytarabine ocfosfate lead to a prolonged exposure of leukemi c cells to this antineoplastic agent during the 14-day cycle. The oral applicability during outpatient treatment and the sustained antineopl astic activity of araC against slowly proliferating leukemic B-cells s uggest that cytarabine ocfosfate might be a useful drug in the treatme nt of chronic lymphocytic leukemia. Four years after diagnosis of B-CL L, a 50-year-old patient was started on cytarabine ocfosfate. Sequenti ally, the patient's disease had proved refractory to treatment with ch lorambucil/prednisone (31 months), fludarabine (5 months), and prednim ustine/mitoxantrone (3 months). These established regimens were discon tinued because of increasing lymphocytosis, significant thrombocytopen ia, and progressive B-symptoms. Following three cycles of cytarabine o cfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombo cytopenia was significantly reduced. The patient has been free of thes e symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 1 4 days with intervals of 14-21 days) for 24 months and remains in an o ngoing partial remission.