Response to cytarabine ocfosfate (YNK01) in a patient with chronic lymphocytic leukemia refractory to treatment with chlorambucil/prednisone, fludarabine, and prednimustine/mitoxantrone

Ann Hematol. 1996 Oct;73(4):201-4. doi: 10.1007/s002770050229.

Abstract

Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the cytotoxic agent cytosine arabinoside (araC) from hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic characteristics of cytarabine ocfosfate lead to a prolonged exposure of leukemic cells to this antineoplasstic agent during the 14-day cycle. the oral applicability during outpatient treatment and the sustained antineoplastic activity of araC against slowly proliferating leukemic B-cells suggest that cytarabine ocfosfate might be a useful drug in the treatment of chronic lymphocytic leukemia. Four years after diagnosis of B-CLL, a 50-year-old patient was started on cytarabine ocfosfate. Sequentially, the patient's disease had proved refractory to treatment with chlorambucil/prednisone (31 months), fludarabine (5 months), and prednimustine/mitoxantrone (3 months). These established regimens were discontinued because of increasing lymphocytosis, significant thrombocytopenia, and progressive B-symptoms. Following three cycles of cytarabine ocfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombocytopenia was significantly reduced. The patient has been free of these symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 14 days with intervals of 14-21 days) for 24 months and remains in an ongoing partial remission.

Publication types

  • Case Reports
  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Administration, Oral
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Arabinonucleotides / pharmacokinetics
  • Arabinonucleotides / therapeutic use*
  • Cytidine Monophosphate / analogs & derivatives*
  • Cytidine Monophosphate / pharmacokinetics
  • Cytidine Monophosphate / therapeutic use
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Male
  • Middle Aged
  • Prodrugs / pharmacokinetics
  • Prodrugs / therapeutic use

Substances

  • Antimetabolites, Antineoplastic
  • Arabinonucleotides
  • Prodrugs
  • 1-arabinofuranosylcytosine-5'-stearylphosphate
  • Cytidine Monophosphate