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.
Department of Hematology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
L E
LE
Robertson
R
R
Hall
M J
MJ
Keating
E
E
Estey
H M
HM
Kantarjian
P
P
McLaughlin
F B
FB
Hagemeister
W
W
Plunkett
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