title: FCR and bevacizumab treatment in patients with relapsed chronic lymphocytic leukemia.
abstract: BACKGROUND
  Patients with relapsed chronic lymphocytic leukemia (CLL) often achieve response with chemoimmunotherapy but have short remission durations. Studies have shown that patients with CLL have increased angiogenesis in the microenvironment; levels of proangiogenic growth factors such as VEGF and/or angiopoietin-2 are also elevated. Increased angiogenesis correlates with poor outcome in CLL. Bevacizumab (B) is a humanized monoclonal antibody targeting VEGF-A.
  
  
  METHODS
  In this study, we analyzed whether a combination of bevacizumab with fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy (FCR-B) could improve outcomes in patients with relapsed CLL. Sixty-two patients were enrolled. The median age of the patients was 60 years (range, 31-84 years) and 40% had received >1 prior therapy for CLL. Sixty-one patients were evaluable for toxicity, and 57 were evaluable for response. Six cycles were planned; 36 patients (59%) completed ≥4-6 cycles of the regimen.
  
  
  RESULTS
  The overall response rate was 79%, with 13 (23%) complete remissions (CRs), 8 nodular partial remissions (14%), and 24 partial remissions (43%). The median progression-free survival and overall survival rates were 13.5 and 45 months, respectively. Grade 3 or 4 toxicities included febrile neutropenia (n = 40), infections (n = 21), thrombocytopenia (n = 18) and anemia (n = 9).
  
  
  CONCLUSIONS
  Results with FCR-B were similar to those observed with an historical cohort of relapsed patients treated with FCR.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Preetesh
authors.initials: P
authors.lastname: Jain
authors.forename: Hun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Ohad
authors.initials: O
authors.lastname: Benjamini
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000068258:Bevacizumab; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: FCR; anti-angiogenic therapy; bevacizumab; chemoimmunotherapy; chronic lymphocytic leukemia, CLL