title: Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Fludarabine and cyclophosphamide (FC), which are active in treatment of chronic lymphocytic leukemia (CLL), are synergistic with the monoclonal antibody rituximab in vitro in lymphoma cell lines. A chemoimmunotherapy program consisting of fludarabine, cyclophosphamide, and rituximab (FCR) was developed with the goal of increasing the complete remission (CR) rate in previously untreated CLL patients to >/= 50%.
  
  
  METHODS
  We conducted a single-arm study of FCR as initial therapy in 224 patients with progressive or advanced CLL. Flow cytometry was used to measure residual disease. Results and safety were compared with a previous regimen using FC.
  
  
  RESULTS
  The median age was 58 years; 75 patients (33%) had Rai stage III to IV disease. The CR rate was 70% (95% CI, 63% to 76%), the nodular partial remission rate was 10%, and the partial remission rate was 15%, for an overall response rate of 95% (95% CI, 92% to 98%). Two thirds of patients evaluated with flow cytometry had less than 1% CD5- and CD19-coexpressing cells in bone marrow after therapy. Grade 3 to 4 neutropenia occurred during 52% of courses; major and minor infections were seen in 2.6% and 10% of courses, respectively. One third of the 224 patients had >/= one episode of infection, and 10% had a fever of unknown origin.
  
  
  CONCLUSIONS
  FCR produced a high CR rate in previously untreated CLL. Most patients had no detectable disease on flow cytometry at the end of therapy. Time to treatment failure analysis showed that 69% of patients were projected to be failure free at 4 years (95% CI, 57% to 81%).
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA. mkeating@mdanderson.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: William
authors.initials: W
authors.lastname: Plunkett
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Detry
authors.forename: Alice
authors.initials: A
authors.lastname: Lynn
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
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 / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; 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