Response to cytarabine ocfosfate (YNK01) in a patient with chronic lymphocytic leukemia refractory to treatment with chlorambucil/prednisone, fludarabine, and prednimustine/mitoxantrone.
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.
Department of Internal Medicine, University of Göttingen, Germany.
J
J
Braess
W
W
Kern
M
M
Unterhalt
C C
CC
Kaufmann
B
B
Ramsauer
M
M
Schüssler
A
A
Kaeser-Fröhlich
W
W
Hiddemann
E
E
Schleyer
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001088:Arabinonucleotides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D001088:Arabinonucleotides; D011355:Prodrugs; C061162:1-arabinofuranosylcytosine-5'-stearylphosphate; D003568:Cytidine Monophosphate