Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia.
OBJECTIVE
The efficacy, toxicity, and tolerability of chemoimmunotherapy with the combination of fludarabine, cyclophosphamide, and rituximab (FCR) were evaluated in previously treated patients with chronic lymphocytic leukemia (CLL). The purpose of this study was to improve the complete remission (CR) rate for previously treated patients and evaluate the quality of bone marrow response.


METHODS
One hundred seventy-seven previously treated patients with CLL were evaluated. Treatment consisted of rituximab 375 mg/m(2) day 1 of course 1 and 500 mg/m(2) day 1 of courses 2 to 6; fludarabine 25 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6; and cyclophosphamide 250 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6. Courses were repeated every 4 weeks.


RESULTS
CR was achieved in 25% of 177 patients, and nodular partial remission and partial remission were achieved in 16% and 32% of patients, respectively; the overall response rate was 73%. Twelve (32%) of 37 complete responders tested achieved molecular remission in bone marrow. Univariate and multivariate analyses were used to identify pretreatment patient characteristics associated with CR and overall remission, longer time to progression, and overall survival.


CONCLUSIONS
The FCR regimen was an active and well-tolerated treatment for previously treated patients with CLL. Myelosuppression was the most common toxicity. FCR induced the highest CR rate reported in a clinical trial of previously treated patients with CLL. Furthermore, molecular remissions were achieved in a third of patients achieving CR.
Wierda
William
W
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA. wwierda@mdanderson.org
O'Brien
Susan
S
Wen
Sijin
S
Faderl
Stefan
S
Garcia-Manero
Guillermo
G
Thomas
Deborah
D
Do
Kim-Anh
KA
Cortes
Jorge
J
Koller
Charles
C
Beran
Miloslav
M
Ferrajoli
Alessandra
A
Giles
Francis
F
Lerner
Susan
S
Albitar
Maher
M
Kantarjian
Hagop
H
Keating
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine