title: Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.
  
  
  METHODS
  This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).
  
  
  RESULTS
  After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.
  
  
  CONCLUSIONS
  R-FC significantly improved the outcome of patients with previously treated CLL.
authors.affiliation: Department of Hematology, Medical University of Lodz, Ciolkowskiego 2, Lodz, Poland 93-510. robaktad@csk.umed.lodz.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Philippe
authors.initials: P
authors.lastname: Solal-Céligny
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Javier
authors.initials: J
authors.lastname: Loscertales
authors.forename: John
authors.initials: J
authors.lastname: Catalano
authors.forename: Boris V
authors.initials: BV
authors.lastname: Afanasiev
authors.forename: Loree
authors.initials: L
authors.lastname: Larratt
authors.forename: Christian H
authors.initials: CH
authors.lastname: Geisler
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.forename: Ilya
authors.initials: I
authors.lastname: Zyuzgin
authors.forename: Peter S
authors.initials: PS
authors.lastname: Ganly
authors.forename: Caroline
authors.initials: C
authors.lastname: Dartigeas
authors.forename: András
authors.initials: A
authors.lastname: Rosta
authors.forename: Jörg
authors.initials: J
authors.lastname: Maurer
authors.forename: Myriam
authors.initials: M
authors.lastname: Mendila
authors.forename: M Wayne
authors.initials: MW
authors.lastname: Saville
authors.forename: Nancy
authors.initials: N
authors.lastname: Valente
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wenger
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Moiseev
mesh_terms: 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 / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D019233:Retreatment; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine