High-dose cytosine arabinoside in chronic lymphocytic leukemia: a clinical and pharmacologic analysis.
Twenty-seven patients with B-cell chronic lymphocytic leukemia (CLL) or a related lymphoid malignancy were treated with high-dose cytosine arabinoside (ara-C) at a dosage of 3 gm/m2 administered over 2 hours every 12 hours at one to four doses per course, which were repeated at 4-week intervals. Median patient age was 60 years. Fifty-four percent of CLL patients had Rai stage III or IV disease and the median number of prior therapies was three. Two patients achieved a complete response, five had a partial response, and two had clinical improvement for an overall response rate of 33%. The median duration of response was 9 months. Myelosuppression and infection were the main toxicities. Intracellular levels of the active metabolite ara-C triphosphate varied among patients, but comparisons of pharmacokinetic parameters revealed no significant differences between responders and non-responders. We conclude that high-dose ara-C has modest activity in CLL and that its use in combination with other agents in the treatment of CLL is warranted.
Robertson
L E
LE
Department of Hematology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Hall
R
R
Keating
M J
MJ
Estey
E
E
Kantarjian
H M
HM
McLaughlin
P
P
Hagemeister
F B
FB
Plunkett
W
W
D000368:Aged; D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism; D003561:Cytarabine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate