Fludarabine: a new agent with major activity against chronic lymphocytic leukemia.
Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.
Keating
M J
MJ
Department of Hematology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Kantarjian
H
H
Talpaz
M
M
Redman
J
J
Koller
C
C
Barlogie
B
B
Velasquez
W
W
Plunkett
W
W
Freireich
E J
EJ
McCredie
K B
KB
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001088:Arabinonucleotides / Q000627:therapeutic use*; D004341:Drug Evaluation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D013921:Thrombocytopenia / Q000139:chemically induced; D001084:Vidarabine Phosphate / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D001088:Arabinonucleotides; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate