Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma.
BACKGROUND
The combination of fludarabine, cyclophosphamide, and rituximab (FC-R) shows significant in vitro synergism and may improve patient outcome with little overlapping toxicity.


METHODS
Between December 2000 and June 2005, 77 patients completed therapy after a median of 4 cycles of FC-R (fludarabine at a dose of 25 mg/m2 intravenously [i.v.] on Days 1-3, cyclophosphamide at a dose of 250 mg/m2 i.v. on Days 1-3, and rituximab at a dose of 375 mg/m2 on Day 1). The median age of the patients was 59 years, 65% were male; 31% had previously untreated disease; and 44% had chronic lymphocytic leukemia (CLL), 29% had follicular lymphoma, and 27% other indolent lymphoid malignancies. In addition to standard disease response criteria, patients underwent evaluation using flow cytometric and/or molecular studies.


RESULTS
Objective responses (OR) and complete responses (CR) were observed in 83% and 42%, respectively, of evaluable patients (n=76), respectively. For patients with CLL, the respective OR and CR rates were 100% and 67% as firstline therapy, and 95% and 14% as salvage therapy. For patients with follicular lymphoma, the respective OR and CR rates were 100% and 86% as firstline therapy, and 87% and 67% as salvage therapy. Responders who had no detectable disease on flow cytometric and/or molecular studies experienced prolonged remissions with no recurrences reported at a median 25 months of follow-up. Peripheral stem cell collection using stem cell factor plus granulocyte-colony-stimulating factor was successful in 10 of 13 patients who underwent mobilization (77%).


CONCLUSIONS
FC-R is highly active as initial or salvage therapy in patients with CLL or indolent non-Hodgkin lymphoma. Collection of autologous stem cells during molecular remission is feasible and may facilitate future exploration of high-dose therapy in these patients.
Tam
Constantine S
CS
Leukemia/Lymphoma Service, Hematology Service, Peter MacCallum Cancer Center, The Alfred Hospital, University of Melbourne, Victoria, Australia.
Wolf
Max
M
Prince
H Miles
HM
Januszewicz
E Henry
EH
Westerman
David
D
Lin
Katherine I
KI
Carney
Dennis
D
Seymour
John F
JF
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*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004357:Drug Synergism; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine