title: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA. wwierda@mdanderson.org
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
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*; 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*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine